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1
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Olival A, Vieira SF, Gonçalves VMF, Cunha C, Tiritan ME, Carvalho A, Reis RL, Ferreira H, Neves NM. Erythrocyte-derived liposomes for the treatment of inflammatory diseases. J Drug Target 2022; 30:873-883. [PMID: 35414285 DOI: 10.1080/1061186x.2022.2066107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory activity. The EDLs were prepared using lipids extracted from erythrocyte membranes, which are rich in omega-3 fatty acids with several health benefits. Diclofenac, a widely used anti-inflammatory drug, was incorporated into EDLs in relevant therapeutic concentrations. The EDLs were also functionalized with folic acid to allow their active targeting of M1 macrophages, which are key players in inflammatory processes. In the presence of lipopolysaccharide (LPS)-stimulated macrophages, empty EDLs and EDLs incorporating diclofenac were able to reduce the levels of important pro-inflammatory cytokines, namely interleukin-6 (IL-6; ≈85% and 77%, respectively) and tumor necrosis factor-alpha (TNF-α; ≈64% and 72%, respectively). Strikingly, cytocompatible concentrations of EDLs presented similar effects to dexamethasone, a potent anti-inflammatory drug, in reducing IL-6 and TNF-α concentrations, demonstrating the EDLs potential to be used as bioactive carriers in the treatment of inflammatory diseases.
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Affiliation(s)
- A Olival
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - S F Vieira
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - V M F Gonçalves
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Paredes, Portugal
| | - C Cunha
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.,Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
| | - M E Tiritan
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Paredes, Portugal.,Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.,Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal
| | - A Carvalho
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.,Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
| | - Rui L Reis
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - H Ferreira
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - N M Neves
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
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Tretiakova DS, Vodovozova EL. Liposomes as Adjuvants and Vaccine Delivery Systems. BIOCHEMISTRY (MOSCOW) SUPPLEMENT. SERIES A, MEMBRANE AND CELL BIOLOGY 2022; 16:1-20. [PMID: 35194485 PMCID: PMC8853224 DOI: 10.1134/s1990747822020076] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 09/22/2021] [Accepted: 09/24/2021] [Indexed: 12/12/2022]
Abstract
The review considers liposomes as systems of substantial interest as adjuvant carriers in vaccinology due to their versatility and maximal biocompatibility. Research and development on the use of liposomes and lipid nanoparticles to create subunit vaccines for the prevention and treatment of infectious diseases has been going on for several decades. In recent years, the area has seen serious progress due to the improvement of the technology of industrial production of various high-grade lipids suitable for parenteral administration and the emergence of new technologies and equipment for the production of liposomal preparations. When developing vaccines, it is necessary to take into account how the body’s immune system (innate and adaptive immunity) functions. The review briefly describes some of the fundamental mechanisms underlying the mobilization of immunity when encountering an antigen, as well as the influence of liposome carriers on the processes of internalization of antigens by immunocompetent cells and ways of immune response induction. The results of the studies on the interactions of liposomes with antigen-presenting cells in function of the liposome size, charge, and phase state of the bilayer, which depends on the lipid composition, are often contradictory and should be verified in each specific case. The introduction of immunostimulant components into the composition of liposomal vaccine complexes—ligands of the pathogen-associated molecular pattern receptors—permits modulation of the strength and type of the immune response. The review briefly discusses liposome-based vaccines approved for use in the clinic for the treatment and prevention of infectious diseases, including mRNA-loaded lipid nanoparticles. Examples of liposomal vaccines that undergo various stages of clinical trials are presented.
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Affiliation(s)
- D S Tretiakova
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
| | - E L Vodovozova
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
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3
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Firdaus FZ, Skwarczynski M, Toth I. Developments in Vaccine Adjuvants. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2022; 2412:145-178. [PMID: 34918245 DOI: 10.1007/978-1-0716-1892-9_8] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Vaccines, including subunit, recombinant, and conjugate vaccines, require the use of an immunostimulator/adjuvant for maximum efficacy. Adjuvants not only enhance the strength and longevity of immune responses but may also influence the type of response. In this chapter, we review the adjuvants that are available for use in human vaccines, such as alum, MF59, AS03, and AS01. We extensively discuss their composition, characteristics, mechanism of action, and effects on the immune system. Additionally, we summarize recent trends in adjuvant discovery, providing a brief overview of saponins, TLRs agonists, polysaccharides, nanoparticles, cytokines, and mucosal adjuvants.
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Affiliation(s)
- Farrhana Ziana Firdaus
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Mariusz Skwarczynski
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Istvan Toth
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia. .,Institute of Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia. .,School of Pharmacy, The University of Queensland, Woolloongabba, QLD, Australia.
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Piccione M, Belloni Fortina A, Ferri G, Andolina G, Beretta L, Cividini A, De Marni E, Caroppo F, Citernesi U, Di Liddo R. Xeroderma Pigmentosum: General Aspects and Management. J Pers Med 2021; 11:1146. [PMID: 34834498 PMCID: PMC8624855 DOI: 10.3390/jpm11111146] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Revised: 10/27/2021] [Accepted: 10/28/2021] [Indexed: 01/25/2023] Open
Abstract
Xeroderma Pigmentosum (XP) is a rare genetic syndrome with a defective DNA nucleotide excision repair. It is characterized by (i) an extreme sensitivity to ultraviolet (UV)-induced damages in the skin and eyes; (ii) high risk to develop multiple skin tumours; and (iii) neurologic alterations in the most severe form. To date, the management of XP patients consists of (i) early diagnosis; (ii) a long-life protection from ultraviolet radiation, including avoidance of unnecessary UV exposure, wearing UV blocking clothing, and use of topical sunscreens; and (iii) surgical resections of skin cancers. No curative treatment is available at present. Thus, in the last decade, in order to prevent or delay the progression of the clinical signs of XP, numerous strategies have been proposed and tested, in some cases, with adverse effects. The present review provides an overview of the molecular mechanisms featuring the development of XP and highlights both advantages and disadvantages of the clinical approaches developed throughout the years. The intention of the authors is to sensitize scientists to the crucial aspects of the pathology that could be differently targeted. In this context, the exploration of the process underlining the conception of liposomal nanocarriers is reported to focus the attention on the potentialities of liposomal technology to optimize the administration of chemoprotective agents in XP patients.
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Affiliation(s)
- Monica Piccione
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
| | - Anna Belloni Fortina
- Pediatric Dermatology Unit, Department of Medicine DIMED, University of Padova, 35128 Padova, Italy; (A.B.F.); (F.C.)
| | - Giulia Ferri
- I.R.A. Istituto Ricerche Applicate S.p.A., 20865 Usmate Velate, Italy; (G.F.); (G.A.); (L.B.); (A.C.); (E.D.M.); (U.C.)
| | - Gloria Andolina
- I.R.A. Istituto Ricerche Applicate S.p.A., 20865 Usmate Velate, Italy; (G.F.); (G.A.); (L.B.); (A.C.); (E.D.M.); (U.C.)
| | - Lorenzo Beretta
- I.R.A. Istituto Ricerche Applicate S.p.A., 20865 Usmate Velate, Italy; (G.F.); (G.A.); (L.B.); (A.C.); (E.D.M.); (U.C.)
| | - Andrea Cividini
- I.R.A. Istituto Ricerche Applicate S.p.A., 20865 Usmate Velate, Italy; (G.F.); (G.A.); (L.B.); (A.C.); (E.D.M.); (U.C.)
| | - Emanuele De Marni
- I.R.A. Istituto Ricerche Applicate S.p.A., 20865 Usmate Velate, Italy; (G.F.); (G.A.); (L.B.); (A.C.); (E.D.M.); (U.C.)
| | - Francesca Caroppo
- Pediatric Dermatology Unit, Department of Medicine DIMED, University of Padova, 35128 Padova, Italy; (A.B.F.); (F.C.)
| | - Ugo Citernesi
- I.R.A. Istituto Ricerche Applicate S.p.A., 20865 Usmate Velate, Italy; (G.F.); (G.A.); (L.B.); (A.C.); (E.D.M.); (U.C.)
| | - Rosa Di Liddo
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
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Large DE, Abdelmessih RG, Fink EA, Auguste DT. Liposome composition in drug delivery design, synthesis, characterization, and clinical application. Adv Drug Deliv Rev 2021; 176:113851. [PMID: 34224787 DOI: 10.1016/j.addr.2021.113851] [Citation(s) in RCA: 407] [Impact Index Per Article: 101.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/18/2021] [Accepted: 06/22/2021] [Indexed: 02/07/2023]
Abstract
Liposomal drug delivery represents a highly adaptable therapeutic platform for treating a wide range of diseases. Natural and synthetic lipids, as well as surfactants, are commonly utilized in the synthesis of liposomal drug delivery vehicles. The molecular diversity in the composition of liposomes enables drug delivery with unique physiological functions, such as pH response, prolonged blood circulation, and reduced systemic toxicity. Herein, we discuss the impact of composition on liposome synthesis, function, and clinical utility.
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Herzog C, Van Herck K, Van Damme P. Hepatitis A vaccination and its immunological and epidemiological long-term effects - a review of the evidence. Hum Vaccin Immunother 2021; 17:1496-1519. [PMID: 33325760 PMCID: PMC8078665 DOI: 10.1080/21645515.2020.1819742] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/16/2020] [Accepted: 09/01/2020] [Indexed: 01/11/2023] Open
Abstract
Hepatitis A virus (HAV) infections continue to represent a significant disease burden causing approximately 200 million infections, 30 million symptomatic illnesses and 30,000 deaths each year. Effective and safe hepatitis A vaccines have been available since the early 1990s. Initially developed for individual prophylaxis, HAV vaccines are now increasingly used to control hepatitis A in endemic areas. The human enteral HAV is eradicable in principle, however, HAV eradication is currently not being pursued. Inactivated HAV vaccines are safe and, after two doses, elicit seroprotection in healthy children, adolescents, and young adults for an estimated 30-40 years, if not lifelong, with no need for a later second booster. The long-term effects of the single-dose live-attenuated HAV vaccines are less well documented but available data suggest they are safe and provide long-lasting immunity and protection. A universal mass vaccination strategy (UMV) based on two doses of inactivated vaccine is commonly implemented in endemic countries and eliminates clinical hepatitis A disease in toddlers within a few years. Consequently, older age groups also benefit due to the herd protection effects. Single-dose UMV programs have shown promising outcomes but need to be monitored for many more years in order to document an effective immune memory persistence. In non-endemic countries, prevention efforts need to focus on 'new' risk groups, such as men having sex with men, prisoners, the homeless, and families visiting friends and relatives in endemic countries. This narrative review presents the current evidence regarding the immunological and epidemiological long-term effects of the hepatitis A vaccination and finally discusses emerging issues and areas for research.
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Affiliation(s)
- Christian Herzog
- Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Koen Van Herck
- Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Department of Public Health, Ghent University, Ghent, Belgium
| | - Pierre Van Damme
- Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
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Juszkiewicz K, Sikorski AF, Czogalla A. Building Blocks to Design Liposomal Delivery Systems. Int J Mol Sci 2020; 21:E9559. [PMID: 33334048 PMCID: PMC7765547 DOI: 10.3390/ijms21249559] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/10/2020] [Accepted: 12/14/2020] [Indexed: 02/07/2023] Open
Abstract
The flexibility of liposomal carriers does not just simply rely on their capability to encapsulate various types of therapeutic substances, but also on the large array of components used for designing liposome-based nanoformulations. Each of their components plays a very specific role in the formulation and can be easily replaced whenever a different therapeutic effect is desired. It is tempting to describe this by an analogy to Lego blocks, since a whole set of structures, differing in their features, can be designed using a certain pool of blocks. In this review, we focus on different design strategies, where a broad variety of liposomal components facilitates the attainment of straightforward control over targeting and drug release, which leads to the design of the most promising systems for drug delivery. The key aspects of this block-based architecture became evident after its implementation in our recent works on liposomal carriers of antisense oligonucleotides and statins, which are described in the last chapter of this review.
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Affiliation(s)
- Katarzyna Juszkiewicz
- Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland;
| | - Aleksander F. Sikorski
- Research and Development Center, Regional Specialist Hospital, Kamieńskiego 73a, 51-124 Wroclaw, Poland;
| | - Aleksander Czogalla
- Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland;
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Majumder J, Taratula O, Minko T. Nanocarrier-based systems for targeted and site specific therapeutic delivery. Adv Drug Deliv Rev 2019; 144:57-77. [PMID: 31400350 PMCID: PMC6748653 DOI: 10.1016/j.addr.2019.07.010] [Citation(s) in RCA: 187] [Impact Index Per Article: 31.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 07/02/2019] [Accepted: 07/05/2019] [Indexed: 01/04/2023]
Abstract
Systemic drug delivery methods such as oral or parenteral administration of free drugs possess relatively low treatment efficiency and marked adverse side effects. The use of nanoparticles for drug delivery in most cases substantially enhances drug efficacy, improves pharmacokinetics and drug release and limits their side effects. However, further enhancement in drug efficacy and significant limitation of adverse side effects can be achieved by specific targeting of nanocarrier-based delivery systems especially in combination with local administration. The present review describes major advantages and limitations of organic and inorganic nanocarriers or living cell-based drug and nucleic acid delivery systems. Among these, different nanoparticles, supramolecular gels, therapeutic cells as living drug carriers etc. have emerged as a new frontier in modern medicine.
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Affiliation(s)
- Joydeb Majumder
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA
| | - Oleh Taratula
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR 97201, USA
| | - Tamara Minko
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA; Environmental and Occupational Health Science Institute, Piscataway, NJ 08854, USA.
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Leung AWY, Amador C, Wang LC, Mody UV, Bally MB. What Drives Innovation: The Canadian Touch on Liposomal Therapeutics. Pharmaceutics 2019; 11:pharmaceutics11030124. [PMID: 30884782 PMCID: PMC6471263 DOI: 10.3390/pharmaceutics11030124] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Revised: 03/11/2019] [Accepted: 03/12/2019] [Indexed: 01/09/2023] Open
Abstract
Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40–50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr™, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet®, MyoCet®, Marqibo®, Vyxeos®, and Onpattro™, which are making positive impacts on patients’ health. This review highlights the Canadian contribution to the development of these and other important liposomal technologies that have touched patients. In this review, we try to address the question of what drives innovation: Is it the individual, the teams, the funding, and/or an entrepreneurial spirit that leads to success? From this perspective, it is possible to define how innovation will translate to meaningful commercial ventures and products with impact in the future. We begin with a brief history followed by descriptions of drug delivery technologies influenced by Canadian researchers. We will discuss recent advances in liposomal technologies, including the Metaplex technology from the author’s lab. The latter exemplifies how a nanotechnology platform can be designed based on multidisciplinary groups with expertise in coordination chemistry, nanomedicines, disease, and business to create new therapeutics that can effect better outcomes in patient populations. We conclude that the team is central to the effort; arguing if the team is entrepreneurial and well positioned, the funds needed will be found, but likely not solely in Canada.
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Affiliation(s)
- Ada W Y Leung
- Cuprous Pharmaceuticals Inc., Vancouver, BC V6T 1Z4, Canada.
- Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada.
- Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
| | - Carolyn Amador
- Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
| | - Lin Chuan Wang
- Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
| | - Urmi V Mody
- Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
| | - Marcel B Bally
- Cuprous Pharmaceuticals Inc., Vancouver, BC V6T 1Z4, Canada.
- Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
- Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
- Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
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10
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Dhakal S, Cheng X, Salcido J, Renu S, Bondra K, Lakshmanappa YS, Misch C, Ghimire S, Feliciano-Ruiz N, Hogshead B, Krakowka S, Carson K, McDonough J, Lee CW, Renukaradhya GJ. Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs. Int J Nanomedicine 2018; 13:6699-6715. [PMID: 30425484 PMCID: PMC6205527 DOI: 10.2147/ijn.s178809] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Background Influenza (flu) is a constant threat to humans and animals, and vaccination is one of the most effective ways to mitigate the disease. Due to incomplete protection induced by current flu vaccines, development of novel flu vaccine candidates is warranted to achieve greater efficacy against constantly evolving flu viruses. Methods In the present study, we used liposome nanoparticle (<200 nm diameter)-based subunit flu vaccine containing ten encapsulated highly conserved B and T cell epitope peptides to induce protective immune response against a zoonotic swine influenza A virus (SwIAV) H1N1 challenge infection in a pig model. Furthermore, we used monosodium urate (MSU) crystals as an adjuvant and co-administered the vaccine formulation as an intranasal mist to flu-free nursery pigs, twice at 3-week intervals. Results Liposome peptides flu vaccine delivered with MSU adjuvant improved the hemagglutination inhibition antibody titer and mucosal IgA response against the SwIAV challenge and also against two other highly genetically variant IAVs. Liposomal vaccines also enhanced the frequency of peptides and virus-specific T-helper/memory cells and IFN-γ response. The improved specific cellular and mucosal humoral immune responses in adjuvanted liposomal peptides flu vaccine partially protected pigs from flu-induced fever and pneumonic lesions, and reduced the nasal virus shedding and viral load in the lungs. Conclusion Overall, our study shows great promise for using liposome and MSU adjuvant- based subunit flu vaccine through the intranasal route, and provides scope for future, pre-clinical investigations in a pig model for developing potent human intranasal subunit flu vaccines.
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Affiliation(s)
- Santosh Dhakal
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Xingguo Cheng
- Pharmaceuticals and Bioengineering Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX 78238-0510, USA,
| | - John Salcido
- Pharmaceuticals and Bioengineering Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX 78238-0510, USA,
| | - Sankar Renu
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Kathy Bondra
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Yashavantha Shaan Lakshmanappa
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Christina Misch
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Shristi Ghimire
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Ninoshkaly Feliciano-Ruiz
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Bradley Hogshead
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Steven Krakowka
- The Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Kenneth Carson
- Pharmaceuticals and Bioengineering Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX 78238-0510, USA,
| | - Joseph McDonough
- Pharmaceuticals and Bioengineering Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX 78238-0510, USA,
| | - Chang Won Lee
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
| | - Gourapura J Renukaradhya
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA, .,Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA,
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Lu J, Wang J, Ling D. Surface Engineering of Nanoparticles for Targeted Delivery to Hepatocellular Carcinoma. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2018; 14:1702037. [PMID: 29251419 DOI: 10.1002/smll.201702037] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 10/24/2017] [Indexed: 05/20/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated deaths worldwide. There is a lack of efficient therapy for HCC; the only available first-line systemic drug, sorafenib, can merely improve the average survival by two months. Among the efforts to develop an efficient therapy for HCC, nanomedicine has drawn the most attention, owing to its unique features such as high drug-loading capacity, intrinsic anticancer activities, integrated diagnostic and therapeutic functionalities, and easy surface engineering with targeting ligands. Despite its tremendous advantages, no nanomedicine can be effective unless it successfully targets the tumor site, which is a challenging task. In this review, the features of HCC are described, and the physiological hurdles that prevent nanoparticles from targeting HCC are discussed. Then, the surface physicochemical factors of nanoparticles that can influence targeting efficiency are discussed. Finally, a thorough description of the physiological barriers that nanomedicine must conquer before uptake by HCC cells if possible is provided, as well as the surface engineering approaches to nanomedicine to achieve targeted delivery to HCC cells. The physiological hurdles and corresponding solutions summarized in this review provide a general guide for the rational design of HCC targeting nanomedicine systems.
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Affiliation(s)
- Jingxiong Lu
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310058, China
| | - Jin Wang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310058, China
| | - Daishun Ling
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310058, China
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Solomon D, Gupta N, Mulla NS, Shukla S, Guerrero YA, Gupta V. Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective. AAPS JOURNAL 2017; 19:1669-1681. [PMID: 28924630 DOI: 10.1208/s12248-017-0142-0] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 08/28/2017] [Indexed: 01/20/2023]
Abstract
In the past few years, measurement of drug release from pharmaceutical dosage forms has been a focus of extensive research because the release profile obtained in vitro can give an indication of the drug's performance in vivo. Currently, there are no compendial in vitro release methods designed for liposomes owing to a range of experimental challenges, which has created a major hurdle for both development and regulatory acceptance of liposome-based drug products. In this paper, we review the current techniques that are most often used to assess in vitro drug release from liposomal products; these include the membrane diffusion techniques (dialysis, reverse dialysis, fractional dialysis, and microdialysis), the sample-and-separate approach, the in situ method, the continuous flow, and the modified United States Pharmacopeia methods (USP I and USP IV). We discuss the principles behind each of the methods and the criteria that assist in choosing the most appropriate method for studying drug release from a liposomal formulation. Also, we have included information concerning the current regulatory requirements for liposomal drug products in the United States and in Europe. In light of increasing costs of preclinical and clinical trials, applying a reliable in vitro release method could serve as a proxy to expensive in vivo bioavailability studies. Graphical Abstract Appropriate in-vitro drug release test from liposomal products is important to predict the in-vivo performance.
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Affiliation(s)
- Deepak Solomon
- Research and Development, Neofluidics LLC, 6650 Lusk Blvd, Suite B102, San Diego, California, 92121, USA
| | - Nilesh Gupta
- Research and Development, Neofluidics LLC, 6650 Lusk Blvd, Suite B102, San Diego, California, 92121, USA
| | - Nihal S Mulla
- Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Drake University, 2507 University Ave, Des Moines, Iowa, 50311, USA
| | - Snehal Shukla
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, St. Albert Hall, B14, Queens, New York, 11439, USA
| | - Yadir A Guerrero
- Research and Development, Neofluidics LLC, 6650 Lusk Blvd, Suite B102, San Diego, California, 92121, USA
| | - Vivek Gupta
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, St. Albert Hall, B14, Queens, New York, 11439, USA.
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Radiolabeling and Quantitative In Vivo SPECT/CT Imaging Study of Liposomes Using the Novel Iminothiolane- 99mTc-Tricarbonyl Complex. CONTRAST MEDIA & MOLECULAR IMAGING 2017; 2017:4693417. [PMID: 29097923 PMCID: PMC5612672 DOI: 10.1155/2017/4693417] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Accepted: 05/04/2017] [Indexed: 01/18/2023]
Abstract
The in vivo biodistribution of liposomal formulations greatly influences the pharmacokinetics of these novel drugs; therefore the radioisotope labeling of liposomes and the use of nuclear imaging methods for in vivo studies are of great interest. In the present work, a new procedure for the surface labeling of liposomes is presented using the novel 99mTc-tricarbonyl complex. Liposomes mimicking the composition of two FDA approved liposomal drugs were used. In the first step of the labeling, thiol-groups were formed on the surface of the liposomes using Traut's reagent, which were subsequently used to bind 99mTc-tricarbonyl complex to the liposomal surface. The labeling efficiency determined by size exclusion chromatography was 95%, and the stability of the labeled liposomes in bovine serum was found to be 94% over 2 hours. The obtained specific activity was 50 MBq per 1 μmol lipid which falls among the highest values reported for 99mTc labeling of liposomes. Quantitative in vivo SPECT/CT biodistribution studies revealed distinct differences between the labeled liposomes and the free 99mTc-tricarbonyl, which indicates the in vivo stability of the labeling. As the studied liposomes were non-PEGylated, fast clearance from the blood vessels and high uptake in the liver and spleen were observed.
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Panahi Y, Farshbaf M, Mohammadhosseini M, Mirahadi M, Khalilov R, Saghfi S, Akbarzadeh A. Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2017; 45:788-799. [DOI: 10.1080/21691401.2017.1282496] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Yunes Panahi
- Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Masoud Farshbaf
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mozhdeh Mirahadi
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rovshan Khalilov
- Department of Plant Physiology, Faculty of Biology, Baku State University, Baku, Azerbaijan
- Joint Ukrainian-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
| | - Siamak Saghfi
- Department of Plant Physiology, Faculty of Biology, Baku State University, Baku, Azerbaijan
- Joint Ukrainian-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
| | - Abolfazl Akbarzadeh
- Joint Ukrainian-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Universal Scientific Education and Research Network (USERN), Tabriz, Iran
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Long-term Serologic Follow-up of Children Vaccinated with a Pediatric Formulation of Virosomal Hepatitis A Vaccine Administered With Routine Childhood Vaccines at 12-15 Months of Age. Pediatr Infect Dis J 2016; 35:e220-8. [PMID: 27093164 DOI: 10.1097/inf.0000000000001176] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The aim of this open-label, active-controlled, parallel group, phase 2 follow-up study was to assess the long-term immunogenicity of Epaxal Junior, the pediatric dose of an aluminum-free virosomal inactivated hepatitis A virus (HAV) vaccine, in children receiving routine childhood vaccines (RCV). METHODS Healthy children (12-15 months old, ≥8 kg weight) were randomized (1:1:1) to group A: Epaxal Junior + RCV (day 1); group B: Epaxal Junior (day 1) + RCV (day 29) and group C: Havrix 720 + RCV (day 1). All 3 groups received 2 doses of HAV vaccines 6 months apart. Children who completed the primary study were followed up from 18 months to 7.5 years post booster. RESULTS Of 291/327 randomized children who had completed the primary study, 157 were followed for the 7.5-year analysis (group A: 50; group B: 54; and group C: 53). Of these, 152 children had protective levels of anti-HAV antibodies [≥10 mIU/mL; 98% (group A); 96.3% (group B); 96.2% (group C)]. Anti-HAV geometric mean concentrations were similar in groups A and B at all the time points (1.5-, 2.5-, 3.5-, 5.25- and 7.5-year time point) but slightly lower in group C. Predictions of the median duration of persistence of seroprotective antibody levels, using the linear mixed model were similar in all groups: (group A: 19.1 years, group B: 18.7 years, group C: 17.3 years). CONCLUSIONS Immunization with Epaxal Junior administered with RCVs at 12 months elicited protective response beyond 7.5 years in almost all children. Assessing the kinetic of anti-HAV antibody titers decline over time, the moment to reach antibody concentrations below the accepted protective level may occur earlier than previously estimated.
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Cordeiro AS, Alonso MJ, de la Fuente M. Nanoengineering of vaccines using natural polysaccharides. Biotechnol Adv 2015; 33:1279-93. [PMID: 26049133 PMCID: PMC7127432 DOI: 10.1016/j.biotechadv.2015.05.010] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Revised: 05/29/2015] [Accepted: 05/31/2015] [Indexed: 12/14/2022]
Abstract
Currently, there are over 70 licensed vaccines, which prevent the pathogenesis of around 30 viruses and bacteria. Nevertheless, there are still important challenges in this area, which include the development of more active, non-invasive, and thermo-resistant vaccines. Important biotechnological advances have led to safer subunit antigens, such as proteins, peptides, and nucleic acids. However, their limited immunogenicity has demanded potent adjuvants that can strengthen the immune response. Particulate nanocarriers hold a high potential as adjuvants in vaccination. Due to their pathogen-like size and structure, they can enhance immune responses by mimicking the natural infection process. Additionally, they can be tailored for non-invasive mucosal administration (needle-free vaccination), and control the delivery of the associated antigens to a specific location and for prolonged times, opening room for single-dose vaccination. Moreover, they allow co-association of immunostimulatory molecules to improve the overall adjuvant capacity. The natural and ubiquitous character of polysaccharides, together with their intrinsic immunomodulating properties, their biocompatibility, and biodegradability, justify their interest in the engineering of nanovaccines. In this review, we aim to provide a state-of-the-art overview regarding the application of nanotechnology in vaccine delivery, with a focus on the most recent advances in the development and application of polysaccharide-based antigen nanocarriers.
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Affiliation(s)
- Ana Sara Cordeiro
- Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), School of Pharmacy, University of Santiago de Compostela, Campus Vida, 15706 Santiago de Compostela, Spain; Nano-oncologicals Lab, Translational Medical Oncology group, Health Research Institute of Santiago de Compostela (IDIS), University Hospital Complex of Santiago de Compostela (CHUS), SERGAS, Santiago de Compostela, Spain
| | - María José Alonso
- Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), School of Pharmacy, University of Santiago de Compostela, Campus Vida, 15706 Santiago de Compostela, Spain
| | - María de la Fuente
- Nano-oncologicals Lab, Translational Medical Oncology group, Health Research Institute of Santiago de Compostela (IDIS), University Hospital Complex of Santiago de Compostela (CHUS), SERGAS, Santiago de Compostela, Spain.
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Affiliation(s)
- Bhushan S Pattni
- Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University , Boston, Massachusetts 02115, United States
| | - Vladimir V Chupin
- Laboratory for Advanced Studies of Membrane Proteins, Moscow Institute of Physics and Technology , Dolgoprudny 141700, Russia
| | - Vladimir P Torchilin
- Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University , Boston, Massachusetts 02115, United States.,Department of Biochemistry, Faculty of Science, King Abdulaziz University , Jeddah 21589, Saudi Arabia
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Abstract
Infectious agents generally use mucosal surfaces as entry port to the body thereby necessitating the need of development of mucosal vaccine as vaccination is important for disease avoidance and suppression. Vaccination through mucosal route is a promising strategy to elicit efficient immune response as parentally administered vaccines induce poor mucosal immunity in general. Safety, economy and stability are highly desired with vaccines and this can be achieved with use of delivery cargos. This review focuses on challenges related with mucosal vaccines and use of nanocarriers as suitable cargos to cater the antigen effectively to the desired site. The review also includes different factors which are to be considered regarding the performance of the nanocarriers and clinical status of these systems.
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Natarajan JV, Nugraha C, Ng XW, Venkatraman S. Sustained-release from nanocarriers: a review. J Control Release 2014; 193:122-38. [DOI: 10.1016/j.jconrel.2014.05.029] [Citation(s) in RCA: 135] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 05/10/2014] [Accepted: 05/17/2014] [Indexed: 12/18/2022]
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Hafner A, Lovrić J, Lakoš GP, Pepić I. Nanotherapeutics in the EU: an overview on current state and future directions. Int J Nanomedicine 2014; 9:1005-23. [PMID: 24600222 PMCID: PMC3933707 DOI: 10.2147/ijn.s55359] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The application of nanotechnology in areas of drug delivery and therapy (ie, nanotherapeutics) is envisioned to have a great impact on public health. The ability of nanotherapeutics to provide targeted drug delivery, improve drug solubility, extend drug half-life, improve a drug’s therapeutic index, and reduce a drug’s immunogenicity has resulted in the potential to revolutionize the treatment of many diseases. In this paper, we review the liposome-, nanocrystal-, virosome-, polymer therapeutic-, nanoemulsion-, and nanoparticle-based approaches to nanotherapeutics, which represent the most successful and commercialized categories within the field of nanomedicine. We discuss the regulatory pathway and initiatives endeavoring to ensure the safe and timely clinical translation of emerging nanotherapeutics and realization of health care benefits. Emerging trends are expected to confirm that this nano-concept can exert a macro-impact on patient benefits, treatment options, and the EU economy.
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Affiliation(s)
- Anita Hafner
- Department of Pharmaceutical Technology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Jasmina Lovrić
- Department of Pharmaceutical Technology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Gorana Perina Lakoš
- Medicines Authorisation Division, Agency for Medicinal Products and Medical Devices, Zagreb, Croatia
| | - Ivan Pepić
- Department of Pharmaceutical Technology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia ; Centre for Applied Pharmacy, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
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22
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Herzog C. Surveying adverse event rates: lessons from a virosomal hepatitis A vaccine. Expert Rev Vaccines 2014; 11:383-5. [DOI: 10.1586/erv.12.11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Mishra D, Hubenak JR, Mathur AB. Nanoparticle systems as tools to improve drug delivery and therapeutic efficacy. J Biomed Mater Res A 2013; 101:3646-60. [PMID: 23878102 DOI: 10.1002/jbm.a.34642] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2012] [Revised: 02/04/2013] [Accepted: 02/05/2013] [Indexed: 02/03/2023]
Abstract
Nanoparticle-based drug delivery systems are appealing because, among other properties, they are easily manufactured and have the capacity to encapsulate a wide variety of drugs, many of which are not directly miscible with water. This review classifies nanoparticles into three broad categories based upon material composition: bio-inspired systems, synthetic systems, and inorganic systems. Each has distinct properties suitable for drug delivery applications, including their structure, composition, and pharmacokinetics (including clearance and uptake mechanisms), making each uniquely suitable for certain types of drugs. Furthermore, nanoparticles can be customized, making them ideal for a variety of applications. Advantages and disadvantages of the different systems are discussed. Strategies for improving nanoparticle efficacy include adding targeting agents on the nanoparticle surface, altering the degradation profile to control drug release, or PEGylating the surface to increase circulation times and reduce immediate clearance by the kidneys. The future of nanoparticle systems seems to be focused on further improving overall patient outcome by increasing delivery accuracy to the target area.
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Affiliation(s)
- Deepa Mishra
- Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 602, Houston, Texas, 77030
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Fan Y, Zhang Q. Development of liposomal formulations: From concept to clinical investigations. Asian J Pharm Sci 2013. [DOI: 10.1016/j.ajps.2013.07.010] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
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Brinkhof MWG, Mayorga O, Bock J, Heininger U, Herzog C. Kinetics of maternally acquired anti-hepatitis A antibodies: prediction of waning based on maternal or cord blood antibody levels. Vaccine 2013; 31:1490-5. [PMID: 23328312 DOI: 10.1016/j.vaccine.2013.01.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Revised: 12/06/2012] [Accepted: 01/02/2013] [Indexed: 10/27/2022]
Abstract
BACKGROUND Timing is critical for efficient hepatitis A vaccination in high endemic areas as high levels of maternal IgG antibodies against the hepatitis A virus (HAV) present in the first year of life may impede the vaccine response. OBJECTIVES To describe the kinetics of the decline of anti-HAV maternal antibodies, and to estimate the time of complete loss of maternal antibodies in infants in León, Nicaragua, a region in which almost all mothers are anti-HAV seropositive. METHODS We collected cord blood samples from 99 healthy newborns together with 49 corresponding maternal blood samples, as well as further blood samples at 2 and 7 months of age. Anti-HAV IgG antibody levels were measured by enzyme immunoassay (EIA). We predicted the time when antibodies would fall below 10 mIU/ml, the presumed lowest level of seroprotection. RESULTS Seroprevalence was 100% at birth (GMC 8392 mIU/ml); maternal and cord blood antibody concentrations were similar. The maternal antibody levels of the infants decreased exponentially with age and the half-life of the maternal antibody was estimated to be 40 days. The relationship between the antibody concentration at birth and time until full waning was described as: critical age (months)=3.355+1.969 × log(10)(Ab-level at birth). The survival model estimated that loss of passive immunity will have occurred in 95% of infants by the age of 13.2 months. CONCLUSIONS Complete waning of maternal anti-HAV antibodies may take until early in the second year of life. The here-derived formula relating maternal or cord blood antibody concentrations to the age at which passive immunity is lost may be used to determine the optimal age of childhood HAV vaccination.
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Affiliation(s)
- Martin W G Brinkhof
- Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland
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Correia-Pinto J, Csaba N, Alonso M. Vaccine delivery carriers: Insights and future perspectives. Int J Pharm 2013; 440:27-38. [DOI: 10.1016/j.ijpharm.2012.04.047] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2011] [Revised: 04/16/2012] [Accepted: 04/17/2012] [Indexed: 01/15/2023]
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Watson DS, Endsley AN, Huang L. Design considerations for liposomal vaccines: influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens. Vaccine 2012; 30:2256-72. [PMID: 22306376 DOI: 10.1016/j.vaccine.2012.01.070] [Citation(s) in RCA: 238] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2011] [Revised: 01/19/2012] [Accepted: 01/23/2012] [Indexed: 02/06/2023]
Abstract
Liposomes (phospholipid bilayer vesicles) are versatile and robust delivery systems for induction of antibody and T lymphocyte responses to associated subunit antigens. In the last 15 years, liposome vaccine technology has matured and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation. Given the intensifying interest in liposome-based vaccines, it is important to understand precisely how liposomes interact with the immune system and stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines - method of antigen attachment, lipid composition, bilayer fluidity, particle charge, and other properties - exert dramatic effects on the resulting immune response. Here, we present a comprehensive review of the physicochemical properties of liposomal vaccines and how they influence immune responses. A discussion of novel and emerging immunomodulators that are suitable for inclusion in liposomal vaccines is also presented. Through a comprehensive analysis of the body of liposomal vaccine literature, we enumerate a series of principles that can guide the rational design of liposomal vaccines to elicit immune responses of a desired magnitude and quality. We also identify major unanswered questions in the field, pointing the direction for future study.
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Affiliation(s)
- Douglas S Watson
- Biosciences Division, SRI International, 140 Research Drive, Harrisonburg, VA 22802, United States. [corrected]
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Chang HI, Yeh MK. Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy. Int J Nanomedicine 2011; 7:49-60. [PMID: 22275822 PMCID: PMC3260950 DOI: 10.2147/ijn.s26766] [Citation(s) in RCA: 284] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2011] [Indexed: 01/06/2023] Open
Abstract
Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposome-based drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized.
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Affiliation(s)
- Hsin-I Chang
- Department of Biochemical Science and Technology, National Chia Yi University, Chiayi City, Taiwan
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Abarca K, Ibáñez I, de la Fuente P, Cerda L, Bergeret J, Frösner G, Ibarra H. Immunogenicity and tolerability of a paediatric presentation of a virosomal hepatitis A vaccine in Chilean children aged 1–16 years. Vaccine 2011; 29:8855-62. [DOI: 10.1016/j.vaccine.2011.09.095] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Revised: 09/15/2011] [Accepted: 09/25/2011] [Indexed: 10/16/2022]
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Saksawad R, Likitnukul S, Warachit B, Hanvivatvong O, Poovorawan Y, Puripokai P. Immunogenicity and safety of a pediatric dose virosomal hepatitis A vaccine in Thai HIV-infected children. Vaccine 2011; 29:4735-8. [PMID: 21570433 DOI: 10.1016/j.vaccine.2011.04.091] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2010] [Revised: 04/11/2011] [Accepted: 04/25/2011] [Indexed: 01/09/2023]
Abstract
The immunogenicity and safety of a pediatric dose of a virosomal hepatitis A vaccine (Epaxal®) was evaluated in a group of 45 Thai children with human immunodeficiency virus (HIV) infection, age 2-16 years. Vaccines were administered at 0 and 6 months. Anti-HAV antibody titers were measured at baseline (before injection) 1 and 7 months after primary vaccination. The prevalence of HAV protective antibody in 45 Thai HIV-infected children was 13.6%. The seroprotection rate was 71% at 1 month and 100% at 7 months. The booster dose increased geometric mean concentration (GMC) from 106.5 mIU/ml to 3486.1 mIU/ml. Higher CD4 lymphocyte counts at enrollment was a predictive factor for HAV antibody response. Both doses of Epaxal® were well tolerated. These preliminary data suggest that a pediatric dose of Epaxal® is an effective hepatitis A vaccine for HIV-infected children and should be considered for implementation on a larger scale in the pediatric HIV population.
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Affiliation(s)
- Rachanee Saksawad
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Pratumwan, Bangkok 10330, Thailand
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Real-life versus package insert: a post-marketing study on adverse-event rates of the virosomal hepatitis A vaccine Epaxal® in healthy travellers. Vaccine 2011; 29:5000-6. [PMID: 21569813 DOI: 10.1016/j.vaccine.2011.04.099] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2010] [Revised: 04/12/2011] [Accepted: 04/26/2011] [Indexed: 11/21/2022]
Abstract
There are various methods to collect adverse events (AEs) in clinical trials. The methods how AEs are collected in vaccine trials is of special interest: solicited reporting can lead to over-reporting events that have little or no biological relationship to the vaccine. We assessed the rate of AEs listed in the package insert for the virosomal hepatitis A vaccine Epaxal(®), comparing data collected by solicited or unsolicited self-reporting. In an open, multi-centre post-marketing study, 2675 healthy travellers received single doses of vaccine administered intramuscularly. AEs were recorded based on solicited and unsolicited questioning during a four-day period after vaccination. A total of 2541 questionnaires could be evaluated (95.0% return rate). Solicited self-reporting resulted in significantly higher (p<0.0001) rates of subjects with AEs than unsolicited reporting, both at baseline (18.9% solicited versus 2.1% unsolicited systemic AEs) and following immunization (29.6% versus 19.3% local AEs; 33.8% versus 18.2% systemic AEs). This could indicate that actual reporting rates of AEs with Epaxal(®) may be substantially lower than described in the package insert. The distribution of AEs differed significantly between the applied methods of collecting AEs. The most common AEs listed in the package insert were reported almost exclusively with solicited questioning. The reporting of local AEs was more likely than that of systemic AEs to be influenced by subjects' sex, age and study centre. Women reported higher rates of AEs than men. The results highlight the need for detailing the methods how vaccine tolerability was reported and assessed.
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Bovier PA, Bock J, Ebengo TF, Frösner G, Glaus J, Herzog C, Loutan L. Predicted 30-year protection after vaccination with an aluminum-free virosomal hepatitis A vaccine. J Med Virol 2010; 82:1629-34. [DOI: 10.1002/jmv.21883] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Stegmann T, Kamphuis T, Meijerhof T, Goud E, de Haan A, Wilschut J. Lipopeptide-adjuvanted respiratory syncytial virus virosomes: A safe and immunogenic non-replicating vaccine formulation. Vaccine 2010; 28:5543-50. [DOI: 10.1016/j.vaccine.2010.06.041] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2010] [Revised: 05/19/2010] [Accepted: 06/10/2010] [Indexed: 11/29/2022]
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Abstract
Among the several drug delivery systems, liposomes--phospholipid nanosized vesicles with a bilayered membrane structure--have drawn a lot of interest as advanced and versatile pharmaceutical carriers for both low and high molecular weight pharmaceuticals. At present, liposomal formulations span multiple areas, from clinical application of the liposomal drugs to the development of various multifunctional liposomal systems to be used in therapy and diagnostics. This chapter provides a brief overview of various liposomal products currently under development at experimental and preclinical level.
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Affiliation(s)
- Tamer A Elbayoumi
- Department of Pharmaceutical Sciences, College of Pharmacy Glendale, Midwestern University, Glendale, AZ, USA
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Frösner G, Steffen R, Herzog C. Virosomal hepatitis a vaccine: comparing intradermal and subcutaneous with intramuscular administration. J Travel Med 2009; 16:413-9. [PMID: 19930383 DOI: 10.1111/j.1708-8305.2009.00351.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.). METHODS Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded. RESULTS Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m. CONCLUSIONS The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.
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Affiliation(s)
- Gert Frösner
- Department of Virology, Max von Pettenkofer-Institute, Ludwig-Maximilians-University Munich, Germany
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Abstract
Over the last few decades, different types of inactivated hepatitis A virus (HAV) vaccines have been developed: several aluminum-adjuvanted vaccines and an aluminum-free, virosome-formulated vaccine. Both types of vaccines are whole-virus preparations that are produced by growth of HAV strains in human diploid cell cultures and are subsequently inactivated with formaldehyde. This review summarizes all published papers on a virosome-formulated vaccine, Epaxal, based on formalin inactivated HAV (strain RG-SB) adsorbed to the surface of special liposomes (virosomes), that replace aluminum hydroxide as the adjuvant principle. A single injection of virosomal HAV vaccine is well tolerated and highly immunogenic, with 88-97% of seroprotection 2 weeks after a first dose. HAV virosomal vaccine can be administered concomitantly with other vaccines, without inducing antigenic competition. Direct comparison with aluminum-adsorbed vaccine has shown that the immunogenicity was similar, but fewer local reactions were reported with Epaxal. Recent studies in children have demonstrated that Epaxal Junior is also an excellent HAV vaccine for mass vaccination programs.
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Affiliation(s)
- Patrick A Bovier
- Department of Community and Primary Care Medicine, Geneva University Hospitals, Switzerland.
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Giovanetti F. Immunisation of the travelling child. Travel Med Infect Dis 2007; 5:349-64. [PMID: 17983974 DOI: 10.1016/j.tmaid.2007.09.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2007] [Accepted: 09/13/2007] [Indexed: 11/30/2022]
Abstract
As a direct consequence of the current increase in international mobility, a significant increase in family travel is occurring. Protection against vaccine preventable diseases in the travelling child plays a key role both from an individual and a public health perspective: pre-travel immunisation protects travelling children and, at the same time, prevents the importation of pathogens that can spread throughout the community. Children immunisation presents unique challenges in travel medicine practice: some vaccines cannot be given below a definite age for several reasons and altering the standard schedule of routine vaccines is sometimes needed to ensure early protection. Furthermore, the risk for some travel-related diseases is higher among children. The aim of this review is to analyse the main epidemiological and clinical aspects relevant to immunisation of travelling children and to provide travel medicine practitioners with a practical approach to this issue.
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Affiliation(s)
- Franco Giovanetti
- Azienda Sanitaria Locale Alba Bra, Dipartimento di Prevenzione, via Vida 10, 12051 Alba, Italy.
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Dagan R, Amir J, Livni G, Greenberg D, Abu-Abed J, Guy L, Ashkenazi S, Foresner G, Froesner G, Tewald F, Schätzl HM, Schaetzl HM, Hoffmann D, Ibanez R, Herzog C. Concomitant administration of a virosome-adjuvanted hepatitis a vaccine with routine childhood vaccines at age twelve to fifteen months: a randomized controlled trial. Pediatr Infect Dis J 2007; 26:787-93. [PMID: 17721372 DOI: 10.1097/inf.0b013e318060acbd] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The objectives of this trial were to test for noninferiority of a virosomal hepatitis A virus (HAV) vaccine (Epaxal) coadministered with routine childhood vaccines compared with Epaxal given alone and to an alum-adjuvanted HAV vaccine (Havrix Junior) coadministered with routine childhood vaccines. METHODS Healthy children 12- to 15-month-old were randomized to receive either a pediatric dose (0.25 mL) of Epaxal coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 109; group A), or Epaxal given alone (n = 105; group B), or Havrix Junior coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 108; group C). A booster dose was given 6 months later. Anti-HAV antibodies were tested before and 1 month after each vaccination. Safety was assessed for 1 month after each vaccination. Solicited adverse events were assessed for 4 days after each vaccination. RESULTS : HAV seroprotection rates (> or =20 mIU/mL) at 1 and 6 months after first dose were: A: 94.2% and 87.5%, B: 92.6% and 80.0%, C: 78.2% and 71.3%, respectively (A versus C: P < 0.001 and P = 0.017 at month 1 and 6, respectively). The respective geometric mean concentrations were: A: 51 and 64 mIU/mL, B: 49 and 59 mIU/mL, C: 33 and 37 mIU/mL (A versus C: P < 0.001 at both time points). All groups achieved 100% seroprotection after the booster dose. The geometric mean concentrations after the booster dose were 1758, 1662, and 1414, for groups A, B and C, respectively (A versus C: P = 0.15). No clinically significant reduction in immune response to all concomitant vaccine antigens was seen. All vaccines were well tolerated. CONCLUSIONS : Coadministration of pediatric Epaxal with routine childhood vaccines showed immunogenicity and safety equal to Epaxal alone as well as to Havrix Junior. After first dose, Epaxal was significantly more immunogenic than Havrix Junior.
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Affiliation(s)
- Ron Dagan
- Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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Van Der Wielen M, Vertruyen A, Froesner G, Ibáñez R, Hunt M, Herzog C, Van Damme P. Immunogenicity and safety of a pediatric dose of a virosome-adjuvanted hepatitis A vaccine: a controlled trial in children aged 1-16 years. Pediatr Infect Dis J 2007; 26:705-10. [PMID: 17848882 DOI: 10.1097/inf.0b013e31806215c8] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The availability of pediatric formulations of hepatitis A virus (HAV) vaccines would facilitate the introduction of universal mass vaccination against HAV. The objective of this study was to compare a pediatric dose (0.25 mL) of Epaxal, a virosomal, aluminum-free HAV vaccine, to 0.5 mL standard dose, and to alum-adsorbed HAV vaccine. METHODS Subjects aged 1-16 years, stratified for age, were randomized (2:2:1) into group A (0.25 mL Epaxal), group B (0.5 mL Epaxal), or group C (Havrix Junior). Vaccines were administered at months 0, 6. Seroprotection rates (>or=10 mIU/mL anti-HAV antibodies) were assessed for noninferiority, defined as lower limit of 1-sided 97.5% CI >-10%. Incidence of local solicited adverse events and unsolicited adverse events were recorded. RESULTS Mean age of 308 enrolled subjects was 8.9 years (range, 1.0-17.0 years). All 3 vaccines were highly immunogenic. Noninferiority of group A versus group B and group C with regard to seroprotection was demonstrated after both vaccine doses for the entire study group and for all age subgroups (11-23 months, 2-4, 5-7, 8-10, 11-13, 14-16 years). One month after first vaccination, geometric mean antibody concentrations were 69.0, 83.5, and 50.5 mIU/mL for the 3 groups, respectively (A versus B, P = 0.0208; A versus C, P = 0.0015). Local injection site pain occurred more frequently in group C than in groups A and B. No subjects withdrew from study or reported any vaccine-related serious adverse event. CONCLUSION In children aged 1-16 years, 0.25 mL dose of Epaxal is as immunogenic as standard 0.5 mL dose and Havrix Junior. The aluminum-free vaccine compares favorably to comparator vaccine regarding local reactogenicity.
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Loutan L, Bovier P, Herzog C. Immunogenicity and safety of a virosomal hepatitis A vaccine in HIV-positive patients. Vaccine 2007; 25:6310-2. [PMID: 17640777 DOI: 10.1016/j.vaccine.2007.06.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2007] [Revised: 06/11/2007] [Accepted: 06/11/2007] [Indexed: 01/13/2023]
Abstract
This short report presents results of an open uncontrolled single centre study which evaluated immunogenicity and safety of a virosome-formulated hepatitis A vaccine (Epaxal) in 14 HIV-positive adult patients and 64 healthy adults receiving a primary immunisation and a booster dose 12 months later. Seroconversion rates (> or =20 mIU/mL), geometric mean concentration (GMC) of anti-HAV antibodies, local and systemic adverse events (AEs) were assessed at baseline and at Months 1, 6, 12, and 13. The seroconversion rate was 63.6% at Month 1 and 91.7% at Month 13 in HIV-positive patients versus 93.8 and 100% in healthy adults. The booster dose increased GMCs from 25.5 to 659.2 mIU/mL in HIV-positive patients versus 104 and 2986 mIU/mL in healthy adults. Epaxal was well tolerated by the HIV-positive patients and was at least as immunogenic as reported for aluminium-adsorbed vaccines. In conclusion, Epaxal can be considered an immunogenic and safe hepatitis A vaccine in HIV-positive patients.
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Affiliation(s)
- L Loutan
- Travel and Migration Medicine Unit, Geneva University Hospitals, rue Micheli-du-Crest 24, 1211 Geneva 14, Switzerland
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Rizzetto M, Zoulim F. Viral Hepatitis. TEXTBOOK OF HEPATOLOGY 2007:819-956. [DOI: 10.1002/9780470691861.ch9a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Vidor E. Vaccination of newborns against hepatitis A in the presence of maternally derived antibodies. J Comp Pathol 2007; 137 Suppl 1:S42-5. [PMID: 17555761 DOI: 10.1016/j.jcpa.2007.04.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Infection by hepatitis A virus (HAV) is a significant cause of childhood disease but effective vaccines are available. Naturally acquired anti-HAV antibodies ensure transfer of protective immunity which persists for up to 6 months in the newborn. Such maternal anti-HAV antibodies are able to inhibit the antibody responses in infants vaccinated with inactivated hepatitis A vaccines, although no clinically significant consequences of this are observed. By increasing the number of doses, for example by using a three dose primary vaccination schedule, and by increasing the amount of vaccinal antigen, this interfering effect may be partially overcome.
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Affiliation(s)
- E Vidor
- Sanofi Pasteur, Campus Mérieux, 1641 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France.
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Hill DR, Ericsson CD, Pearson RD, Keystone JS, Freedman DO, Kozarsky PE, DuPont HL, Bia FJ, Fischer PR, Ryan ET. The Practice of Travel Medicine: Guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006; 43:1499-539. [PMID: 17109284 DOI: 10.1086/508782] [Citation(s) in RCA: 137] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2006] [Accepted: 08/23/2006] [Indexed: 12/17/2022] Open
Affiliation(s)
- David R Hill
- National Travel Health Network and Centre, London School of Hygiene and Tropical Medicine, London, WC1E 6AU, England.
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López EL, Contrini MM, Xifró MC, Cattaneo MA, Zambrano B, Dumas R, Rouyrre N, Weber F. Hepatitis A vaccination of Argentinean infants: comparison of two vaccination schedules. Vaccine 2006; 25:102-8. [PMID: 16914234 DOI: 10.1016/j.vaccine.2006.07.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2005] [Revised: 03/07/2006] [Accepted: 07/07/2006] [Indexed: 10/24/2022]
Abstract
BACKGROUND Early immunization to protect infants against hepatitis A (HA) is recommended in intermediate or high endemic areas of the world, but little is known of the effects of maternal antibodies on the immune response. We studied the immunogenicity and reactogenicity of an inactivated HA vaccine administered in two different schedules to 2-month-old infants in an intermediate/high endemic area in Argentina. METHODS In this double-blind, randomized study 131 infants received either three doses (at 2, 4, 6 months of age [Group A]) or one dose (at 6 months of age [Group B]) of the pediatric inactivated HA vaccine, Avaxim 80, and a booster dose at 15-18 months. HAV antibodies were measured (ELISA) at 2, 7, 15-18 and 16-19 months of age. Immediate (30 min after injection) and solicited local and systemic reactions were recorded for 7 days after each injection. RESULTS Of 107/131 subjects (81.6%) who completed the study and who provided final serum samples after booster dose, 94 (87.8%) were seropositive at enrolment (>20 mIU/mL) with geometric mean concentrations (GMC) of 2989 and 3637 mIU/mL in Groups A and B, respectively. One month post-booster GMCs were 8236 mIU/ml (95% CI; 6304, 10760) and 1687 mIU/ml (1148, 2479) in Groups A and B, respectively, with 100% seroprotection. CONCLUSIONS The HA vaccine was well tolerated and induced immunological priming in both groups during the first year of life in spite of the presence of maternal antibodies. Post-booster GMCs achieved after one or three primary doses suggest a long-term protection against HA.
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Affiliation(s)
- E L López
- Hospital de Niños Ricardo Gutiérrez, Guido 2676, Piso 10, 1425 Buenos Aires, Argentina.
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Abstract
Hepatitis A is one of the most common vaccine-preventable infectious diseases in the world. With at least 1.5 million cases of hepatitis A worldwide each year, disease management constitutes a substantial economic burden. The first effective vaccine against hepatitis A, Havrix was introduced in 1992. This review summarizes data accumulated following more than a decade of clinical experience with this vaccine and compares clinical data with other currently available hepatitis A vaccines. Based on this data and on the current immunological knowledge, a recent consensus concluded that hepatitis A vaccines induce lifelong protection, and thus booster vaccinations against hepatitis A are unnecessary in fully immunized, healthy people. In view of this, current regulatory recommendations for the use of hepatitis A vaccines are reviewed and possible future strategies identified.
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Affiliation(s)
- Koen Van Herck
- Centre for the Evaluation of Vaccination, WHO Collaborating Centre for the Prevention and Control of Viral Hepatitis, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
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Abstract
BACKGROUND Protection against hepatitis A virus (HAV) in the elderly is becoming more important as more senior travelers visit areas of high HAV endemicity, and less have protective antibodies acquired after natural infection during childhood. This study assessed the immunogenicity and safety of hepatitis A vaccine in elderly compared to young adults. METHODS In this open, uncontrolled study, subjects of 18 to 45 years or < or = 50 years of age received two doses of aluminum-free, virosomal HAV vaccine, Epaxal (Berna Biotech Ltd, formerly Swiss Serum and Vaccine Institute, Bern, Switzerland) 12 months apart. RESULTS After both the basic and the booster doses, geometric mean titers (GMT) for anti-HAV antibodies were 1.7-fold higher in subjects younger than 45 years compared with those < or = 50 years of age. The proportional increase in GMT after the booster dose, however, was similar in younger and older subjects. Seroprotection (< or = 20 mIU/mL) rates in the younger and older subjects were 100 and 65%, respectively, after the first vaccination and 100 and 97%, respectively, after the booster dose. Systemic and local adverse events were mainly mild and short-lived. CONCLUSION These data show that HAV virosomal vaccine (Epaxal) is well tolerated and immunogenic in elderly subjects. The clinical relevance of lower seroconversion rates after the primary dose is unknown in this population of travelers.
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Abstract
PURPOSE OF REVIEW To concisely review data published over the past year on three topics pertinent to the practicing pediatrician: immunizations, neonatal jaundice, and animal-induced injuries. RECENT FINDINGS Updates on immunizations, including varicella and pneumococcus in the post-vaccine era, use of a polyvalent conjugated meningococcal vaccine, and influenza vaccination during a vaccine shortage are discussed. Mortality and morbidity from varicella, and risk of invasive disease from pneumococcal infections have declined. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention released guidelines for the use of a tetravalent meningococcal conjugate vaccine in adolescents 11 years and older. Infants at younger gestational age are at higher risk for developing hyperbilirubinemia. The American Academy of Pediatrics has released new guidelines emphasizing breastfeeding, systematic pre-discharge assessment for risk factors, early follow-up and intervention. Use of home nursing services in the postnatal period is cost-effective. Although the incidence of rabies is low, many receive postexposure prophylaxis. Spider bites cause fewer systemic effects in children than adults. Pet reptile carriage of salmonella necessitates handwashing after handling of animals. SUMMARY Recommendations for adolescent meningococcal vaccination, and the impact of varicella and pneumococcal immunization on our communities reflect an evolution in our management of infectious diseases. The latest practice guidelines on hyperbilirubinemia emphasize close follow-up of all newborns after postpartum discharge and even more careful evaluation of those infants near term. Education on rabies prophylaxis, spider bites, and salmonella from pet reptiles should focus on judicious use of resources and the proper handling of pets.
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Affiliation(s)
- Melissa S Lee
- Harvard Combined Program in Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
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Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 2005. [DOI: 10.1038/nrd1632 and 3724=3724-- lkhg] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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