Human monkeypox (Mpox) is a zoonotic disease caused by monkeypox virus (MPXV) present in western Africa and exported sporadically worldwide. MPXV causes illness in individuals and pregnant women which constitute a population at risk with obstetrical and fetal complications including miscarriage, stillbirth and premature delivery. There are accumulated data suggesting a vertical transmission of MPXV from mother to fetus. This review provides an overview of the literature on MPXV infection in pregnant women with a specific focus on vertical transmission.

The data on immune responses of individuals undergoing modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccination are scarce. We aimed to compare Mpox virus-specific antibody and neutralizing antibody responses among people with and those without HIV receiving MVA-BN vaccines.

This prospective study enrolled participants undergoing two-dose MVA-BN vaccination to investigate seroresponses after vaccination. Blood samples were collected before and after each dose of vaccination for determinations of anti-A29 and anti-H3 IgG. Neutralization tests were conducted for samples tested positive for both anti-A29 and anti-H3 IgG.

Overall, 441 participants undergoing two-dose MVA-BN vaccination were enrolled. Seroconversion for anti-A29 and anti-H3 IgG, respectively, after the second dose of vaccination was 18.2% and 61.2%, 10.9% and 65.0%, and 51.6% and 90.6% among people with HIV, people without HIV, and those who had had smallpox vaccination previously, respectively. About 20% of the participants with seroconversion lost seroresponses after a 7-month period of observation. None of the serum samples from vaccinated participants demonstrated neutralizing ability.

Participants with previous smallpox vaccination had higher and more sustained antibody responses after receiving two doses of MVA-BN vaccines than those who had not undergone smallpox vaccination. More studies are warranted to assess the seroresponses to booster MVA-BN vaccination for vaccine nonresponders or those having lost seroresponses.

Monkeypox (Mpox), a zoonotic viral disease caused by the Mpox virus (MPOXV), was first identified in 1958 and remained largely confined to Central and West Africa for decades. While it usually exhibited limited international transmission, recent outbreaks, including in the USA in 2003 and globally in 2024, highlight significant epidemiological shifts. We aimed to systematically evaluate the evolution of Mpox from 1958 to 2024, focussing on its epidemiology, viral evolution, and public health responses.

We conducted a systematic review using data from global health reports, surveillance databases, and published literature. The analysis covered key outbreaks, transmission patterns, geographic distribution, public health responses, and the roles of viral mutations and vaccination in disease management.

The 2022 Mpox outbreak, declared a Public Health Emergency of International Concern by the World Health Organization (WHO), was characterised by an unprecedented international spread of the virus. By July 2024, a total of 102 997 confirmed cases and 223 deaths were reported across 121 countries. Two distinct viral clades were identified: Central African (clade I) and West African (clade II), with the latter being the primary agent of global transmission. Research on Mpox has highlighted the protective effects of smallpox vaccination and emerging risk factors such as human-animal interactions and international travel.

Mpox has evolved from a regionally contained zoonotic disease to a global public health challenge. Enhanced surveillance, international collaboration, and targeted interventions in non-endemic regions are critical for mitigating future outbreaks and managing ongoing epidemiological changes.

In May 2022, the most widespread outbreak of sustained transmission of mpox outside of countries historically affected countries in Western and Central Africa occurred. We aimed to examine the personal and clinical experiences of international healthcare workers (HCWs) during this public health emergency. We conducted an international cross-sectional survey study between August and October 2022, examining the experiences and perceptions of HCWs clinically involved in the 2022 mpox response. Respondents were recruited via an international network of sexual health and HIV clinicians responding to mpox and promoted through clinical associations and social media. Survey domains included: clinical workload; preparedness; training and support at work; psychological well-being and vaccination. 725 multi-national healthcare workers across 41 countries were included in the analysis. 91% were physicians specialised in Sexual Health or Infectious Diseases; with 34% (n = 247) of all respondents involved in mpox policy. A substantial proportion of respondents (n = 296, 41%) reported working longer hours during the mpox outbreak, with no concomitant removal of other clinical responsibilities. 30% (n = 218) of respondents reported that they had never heard of mpox before the outbreak and over 25% of the respondents reported that they had misdiagnosed someone initially. This culminated in a high prevalence of moral distress at thirty percent. Less than 9% of HCWs in the region of the Caribbean, Central America and South America had been offered a vaccine as compared to almost one-third in the other regions. Where offered, there were high levels of uptake across all regions. The findings highlight a critical need for addressing the profound gaps in HCW knowledge about re-emerging diseases with pandemic potential. Strengthening the resilience of global health systems and prioritising internationally coordinated approaches to global vaccine deployment is imperative.

The decline in cross-protection provided by the smallpox vaccine increases the risk of infection from other poxviruses. While drug combinations are a promising management, they remain underdeveloped for poxviruses. Prior to the development of the smallpox vaccine, China had long relied on herbal medicine to combat pox and accumulated a wealth of knowledge regarding different herb combinations and symptoms related to pox. The information was documented in the form of prescriptions.

The extensive data of prescriptions offer the potential for uncovering commonalities underlying these prescriptions, thereby providing valuable insights into the development of drug combinations against pox.

The 2344 prescriptions were collected from the LTM-TCM database and 12 traditional Chinese medicine books. Firstly, the relative frequency of citation was utilized to identify the most used herbs among these prescriptions. TCMSP and LTM-TCM databases were employed to gather information about active compounds and their targets. GeneCards and DisGeNET databases were utilized to determine the associated targets for smallpox, cowpox, chickenpox, and mpox. Subsequently, network pharmacology analysis was conducted to investigate potential pathway information related to the most used herbs. A comparison of active compounds from these herbs resulted in the identification of 29 high-frequency compounds. The functions of these compounds were elucidated through gene overlap analysis, docking, and literature review. Finally, we summarized pox-related symptoms and used fidelity levels to distinguish specific herbs for corresponding symptoms.

Based on 2344 traditional pox-related prescriptions, we identified 19 most used herbs and 64 associated bio-functional modules for poxvirus treatment, with the most significant one being immunoregulation primarily involving CD4+ regulation. We also identified 29 leads that possess anti-inflammatory, antimicrobial, and antiviral properties. These herbs and leads hold the potential for pox treatment. Additionally, docking analysis suggested that these leads could inhibit poxvirus DNA synthesis, RNA capping machinery processes, and mature poxvirus particle formation, as well as immunosuppressors. The clinical features of mpox in 2022 were found to align well with our description of symptoms related to the pox.

Through the analysis of 2344 prescriptions for pox treatment, we obtained a comprehensive library of the most used herbs and high-frequency compounds, along with their potential functional spectrum. These libraries served as raw resources for drug combination development, while the identified symptom patterns and specific herbs greatly enhanced our insight into diverse treatments for pox patients.

Since May 2022, the global spread of monkeypox virus (MPXV) has presented a significant threat to public health. Despite this, there are limited preventive measures available. In this study, different computational tools were employed to design a multi-epitope vaccine targeting MPXV. Three key MPXV proteins, M1R, B6R, and F3L, were chosen for epitope selection, guided by bioinformatic analyses to identify immunodominant epitopes for T- and B-cell activation. To enhance immune stimulation and facilitate targeted delivery of the vaccine to specific cells, the selected epitopes were linked to novel carriers, including the extracellular domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a 12-mer Clec9a binding peptide (CBP-12), and a Toll-like receptor 2 (TLR2) peptide ligand. The designed vaccine construct exhibited strong antigenicity along with nonallergenic and nontoxic properties, with favorable physicochemical characteristics. The validated vaccine's tertiary structure underwent evaluation for interactions with CD80/86, Clec9a, and TLR2 through molecular docking and molecular dynamics simulation. The results ensured the vaccine's stability and high affinity for the aforementioned receptors. In silico immune simulations studies revealed robust innate and adaptive immune responses, including enhanced mucosal immunity essential for protection against MPXV. Ultimately, the DNA sequence of the vaccine construct was synthesized and successfully cloned into the pET-22b(+) vector. Our study, through integration of computational predictions, suggests the proposed vaccine's potential efficacy in safeguarding against MPXV; however, further in vitro and in vivo validations are imperative to assess real-world effectiveness and safety.

Disparities in vaccine coverage among groups in the USA is common, possibly due to higher vaccine hesitancy in certain populations, difficulty accessing vaccines, and underlying social vulnerability.

The aim of this study was to investigate the association between mpox vaccine administration, social determinants of health, and social vulnerability index (SVI) in Durham County, North Carolina, USA. Random forest regression (RFE) and min-max scaling preprocessing were used to predict mpox vaccinations in Durham County at the census tract level. The top eleven most influential features and their correlations with mpox vaccination were calculated.

Non-Hispanic white individuals, males, and those between the ages of 20 and 40 years were overrepresented in mpox vaccine reception in Durham County. Surprisingly, lacking a high school diploma, lacking health insurance, lacking a household vehicle, and living below the poverty line were all positively associated with receiving the mpox vaccine. Being a Black or African American and Hispanic or Latino individual was also positively associated with receiving the mpox vaccine.

Vaccine outreach efforts in Durham County, North Carolina, had success in reaching at-risk individuals, including socially vulnerable individuals. Future research should focus more specifically on how social vulnerability relates to vaccine reception for vaccine-preventable diseases.

The monkeypox outbreak has grown beyond the regions in which it was considered endemic. It has spread from central and west Africa to non-endemic regions like Europe, America, and other parts of the world. It has recently been classified as a public health emergency of international concern. This study evaluated the challenges faced globally and equitable access to monkeypox vaccines. Global competition has been observed in the race to obtain vaccines, with low- and middle-income countries being disadvantaged. Great inequity exists in the distribution of vaccines globally through advance purchase agreements, vaccine stockpiling, vaccine nationalism, the inequitable distribution of existing resources, and insufficient surveillance and reporting mechanisms. To address some of these challenges, there is a need for strengthening the global vaccine manufacturing capacity, targeting countries with elevated risk profiles and limited resources, strengthening surveillance systems, and addressing vaccine hesitancy.

Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects.

We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV.

The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R + sM1R + sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35 + M1 + B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice.

Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines.

National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.

In 2022, the global outbreak of monkeypox virus (MPXV) with increased human-to-human transmission triggered urgent public health interventions. Plant-derived monoclonal antibodies (mAbs) are being explored as potential therapeutic strategies due to their diverse mechanisms of antiviral activity. MPXV produces two key infectious particles: the mature virion (MV) and the extracellular enveloped virion (EV), both essential for infection and spread. Effective therapies must target both to halt replication and transmission. Our prior research demonstrated the development of a potent neutralizing mAb against MPXV MV. This study focuses on developing a plant-derived mAb targeting MPXV EV, which is critical for viral dissemination within the host and generally resistant to antibody neutralization. Our findings reveal that the mAb (H2) can be robustly produced in Nicotiana benthamiana plants via transient expression. The plant-made H2 mAb effectively targets MPXV EV by binding specifically to the A35 MPXV antigen. Importantly, H2 mAb shows notable neutralizing activity against the infectious MPXV EV particle. This investigation is the first to report the development of a plant-derived anti-EV mAb for MPXV prevention and treatment, as well as the first demonstration of anti-MPXV EV activity by an mAb across any production platform. It highlights the potential of plant-produced mAbs as therapeutics for emerging infectious diseases, including the MPXV outbreak.

Monkeypox virus (MPV) infection has developed into a re-emerging disease, and despite the potential of tecovirimat and cidofovir drugs, there is currently no conclusive treatment. The treatment's effectiveness and cost challenges motivate us to use In Silico approaches to seek natural compounds as candidate antiviral inhibitors. Using Maestro 11.5 in Schrodinger suite 2018, available natural molecules with validated chemical structures collected from Eximed Laboratory were subjected to molecular docking and ADMET analysis against the highly conserved A42R Profilin-like Protein of Monkeypox Virus Zaire-96-I-16 (PDB: 4QWO) with resolution of 1.52 Å solved 3D structure. Compared to the FDA-approved Tecovirimat, molecular docking revealed that Salsoline derivatives, Genistein, Semisynthetic derivative of kojic acid, and Naringenin had strengthened affinity (-8.9 to -10 kcal/mol) to 4QWO, and the molecular dynamic's simulation confirmed their high binding stability. In support of these results, the hydrogen bond analysis indicated that the Salsoline derivative had the most robust interaction with the binding pockets of 4QWO among the four molecules. Moreover, the comparative free energy analyses using MM-PBSA revealed an average binding free energy of the complexes of Salsoline derivative, Genistein, Semisynthetic derivative of kojic acid, Naringenin, of -106.418, -46.808, -50.770, and -63.319 kJ/mol, respectively which are lower than -33.855 kJ/mol of the Tecovirimat complex. Interestingly, these results and the ADMET predictions suggest that the four compounds are promising inhibitors of 4QWO, which agrees with previous results showing their antiviral activities against other viruses.

Due to the authorization of the Mpox vaccines, we aimed to identify determinants of the intention to get vaccinated, actively trying to receive vaccination, and for successfully receiving a vaccination in Germany employing the 5 C model of vaccination readiness.

Data stem from a cross-sectional online survey that was available online from August 13, 2022 to August 31, 2022. To assess the influence of the 5 C Model on vaccination behavior, we conducted a multinomial logistic regression.

3,338 participants responded to the survey, with 487 already vaccinated and 2,066 intending to receive a vaccination. Confidence and collective responsibility were positively associated with intention to get vaccinated, while complacency was negatively correlated. A higher score on the calculation scale increased the odds of intention to receive vaccination but not with actively having tried to receive a vaccination. Fewer perceived constraints were associated with higher odds to be vaccinated. Patients in practices that focus on HIV treatment were more likely to intend to get vaccinated, to have tried to get vaccinated and to be vaccinated, regardless of indication. While level of education had no impact, having an indication to get vaccinated was a strong predictor of vaccination behavior in all groups.

Future vaccination campaigns should aim to reduce specific constraints of the target group and make vaccines widely available in primary care institutions beyond HIV-focused practices.

Monkeypox is a zoonotic viral disease. Monkeypox was first reported in humans about 54 years ago. Prior to the global outbreak, monkeypox was endemic to the rainforests of central and western African countries. In the last three years, increasing numbers of human monkeypox have been reported from various countries. Responding to the severity, monkeypox was declared a Public Health Emergency of International Concern by the World Health Organization. In the absence of approved drugs or clinical studies, repurposed drugs and therapeutic medical countermeasures effective against other orthopoxviruses have been utilized to treat severe human monkeypox cases. Currently, clinical trials are underway exploring the potential therapeutic effectiveness of tecovirimate in human monkeypox cases. Monoclonal antibodies, IFN-β, resveratrol, and 15 triple-targeting FDA-approved drugs represent potential new drug targets for human monkeypox, necessitating further research.

Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda.

We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648).

Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric case fatality ratio was 11% (95% CI 4-20), I2=75%. Data from 12 pregnancies showed half resulted in fetal death. Research on vaccine and immune globulin safety remains scarce for children and absent for pregnant individuals.

Our review highlights critical knowledge gaps in the epidemiology, prevention, and treatment of mpox in children and pregnant individuals, especially those residing in endemic countries. Increased funding, international collaboration, and equitable research is needed to inform mpox control strategies tailored for at-risk communities in endemic countries.

None.

For the French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Over the past year, an unexpected surge in human monkeypox (hMPX) cases has been observed. This outbreak differs from previous ones, displaying distinct epidemiological characteristics and transmission patterns, believed to be influenced by a newly emerging monkeypox virus (MPXV) lineage. Notably, this emerging MPXV lineage has exhibited several non-synonymous mutations, some of which are linked to immunomodulatory activities and antigenic characteristics that aid in host detection. However, specific treatments or vaccines for human monkeypox are currently lacking. Hence, we aim to develop a multi-epitope mRNA vaccine by using immunoinformatics approaches against the MPXV, particularly its emerging variants. Six proteins (A29L, A35R, B6R, M1R, H3L, and E8L) were chosen for epitope and mutation site identification. Seventeen top-performing epitopes and eight epitopes containing mutation sites were selected and combined with adjuvants, the PADRE sequence, and linkers for vaccine development. The molecular and physical properties of the designed vaccine (WLmpx) were favorable. Immunological characteristics of WLmpx were assessed through molecular docking, molecular dynamics (MD) simulations, and immune simulations. Finally, the vaccine sequence was utilized to formulate an mRNA-based vaccine. The informatics-based predicted results indicated that the designed vaccine exhibits significant potential in eliciting high-level humoral and cellular immune responses, but further validation through in vivo and vitro studies is warranted.

Monkeypox virus (MPXV) is the etiological agent of monkeypox (mpox), a zoonotic disease. MPXV is endemic in the forested regions of West and Central Africa, but the virus has recently spread globally, causing outbreaks in multiple non-endemic countries. In this paper, we review the characteristics of the virus, including its ecology, genomics, infection biology, and evolution. We estimate by phylogenomic molecular clock that the B.1 lineage responsible for the 2022 mpox outbreaks has been in circulation since 2016. We interrogate the host-virus interactions that modulate the virus infection biology, signal transduction, pathogenesis, and host immune responses. We highlight the changing pathophysiology and epidemiology of MPXV and summarize recent advances in the prevention and treatment of mpox. In addition, this review identifies knowledge gaps with respect to the virus and the disease, suggests future research directions to address the knowledge gaps, and proposes a One Health approach as an effective strategy to prevent current and future epidemics of mpox.

Developing protein-based vaccines against bacteria has proved much more challenging than producing similar immunisations against viruses. Currently, anti-bacterial vaccines are designed using methods based on reverse vaccinology. These identify broadly conserved, immunogenic proteins using a combination of genomic and high-throughput laboratory data. While this approach has successfully generated multiple rationally designed formulations that show promising immunogenicity in animal models, few have been licensed. The difficulty of inducing protective immunity in humans with such vaccines mirrors the ability of many bacteria to recolonise individuals despite recognition by natural polyvalent antibody repertoires. As bacteria express too many antigens to evade all adaptive immune responses through mutation, they must instead inhibit the efficacy of such host defences through expressing surface structures that interface with the immune system. Therefore, 'immune interface interference' (I3) vaccines that target these features should synergistically directly target bacteria and prevent them from inhibiting responses to other surface antigens. This approach may help us understand the efficacy of the two recently introduced immunisations against serotype B meningococci, which both target the Factor H-binding protein (fHbp) that inhibits complement deposition on the bacterial surface. Therefore, I3 vaccine designs may help overcome the current challenges of developing protein-based vaccines to prevent bacterial infections.

The human monkeypox virus (Mpox) is classified as a member of the Poxviridae family and belongs to the Orthopoxvirus genus. Mpox possesses double-stranded DNA, and there are two known genetic clades: those originating in West Africa and the Congo Basin, commonly known as Central African clades. Mpox may be treated with either the vaccinia vaccination or the therapeutics. Modifying the smallpox vaccine for treating and preventing Mpox has shown to be beneficial because of the strong link between smallpox and Mpox viruses and their categorization in the same family. Cross-protection against Mpox is effective with two Food and Drug Administration (FDA)-approved smallpox vaccines (ACAM2000 and JYNNEOSTM). However, ACAM2000 has the potential for significant adverse effects, such as cardiac issues, whereas JYNNEOS has a lower risk profile. Moreover, Mpox has managed to resurface, although with modified characteristics, due to the discontinuation and cessation of the smallpox vaccine for 40 years. The safety and efficacy of the two leading mRNA vaccines against SARS-CoV-2 and its many variants have been shown in clinical trials and subsequent data analysis. This first mRNA treatment model involves injecting patients with messenger RNA to produce target proteins and elicit an immunological response. High potency, the possibility of safe administration, low-cost manufacture, and quick development is just a few of the benefits of RNA-based vaccines that pave the way for a viable alternative to conventional vaccines. When protecting against Mpox infection, mRNA vaccines are pretty efficient and may one day replace the present whole-virus vaccines. Therefore, the purpose of this article is to provide a synopsis of the ongoing research, development, and testing of an mRNA vaccine against Mpox.

The Monkeypox virus, an Orthopoxvirus with zoonotic origins, has been responsible for a growing number of human infections reminiscent of smallpox since May 2022, as reported by the World Health Organization. As of now, there are no established medical treatments for managing Monkeypox infections. In this study, we used machine learning to select conserved epitopes. Proteins were determined using Reverse Vaccinology and Gene Ontology subcellular localization, and their epitopes were predicted. NextClade was used to calculate the number of mutations in each amino acid position using 2433 Monkeypox sequences. The Unsupervised Nearest Neighbor machine learning algorithm and ideal matrix [0 0] were used to calculate the conservancy score of epitopes. Six proteins were determined for epitope prediction. Finally, 47 MHC-I epitopes, 5 MHC-II epitopes, and 10 Linear B cell epitopes were discovered. Our method can select epitopes for vaccine design to prevent viruses with accelerated evolution and high mutation rate.

Wastewater surveillance has emerged recently as a powerful approach to understanding infectious disease dynamics in densely populated zones. Wastewater surveillance, while promising as a public health tool, is often hampered by slow turn-around times, complex analytical protocols, and resource-intensive techniques. In this study, we evaluated an affinity capture method and microfluidic digital PCR as a rapid approach to quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mpox (formerly known as monkeypox) virus, and fecal indicator, pepper mild mottle virus (PMMoV) in wastewater during a mass-gathering event. Wastewater samples (n = 131) were collected from residential and commercial manholes, pump stations, and a city's wastewater treatment plant. The use of Nanotrap® Microbiome Particles and microfluidic digital PCR produced comparable results to other established methodologies, with reduced process complexity and analytical times, providing same day results for public health preparedness and response. Using indigenous SARS-CoV-2 and PMMoV in wastewater, the average viral recovery efficiency was estimated at 10.1 %. Both SARS-CoV-2 N1 and N2 genes were consistently detected throughout the sampling period, with increased RNA concentrations mainly in wastewater samples collected from commercial area after festival mass gatherings. The mpox virus was sporadically detected in wastewater samples during the surveillance period, without distinct temporal trends. SARS-CoV-2 RNA concentrations in the city's wastewater mirrored the city's COVID-19 cases, confirming the predictive properties of wastewater surveillance. Wastewater surveillance continues to be beneficial for tracking diseases that display gastrointestinal symptoms, including SARS-CoV-2, and can be a powerful tool for sentinel surveillance. However, careful site selection and a thorough understanding of community dynamics are necessary when performing targeted surveillance during temporary mass-gathering events as potential confirmation bias may occur.

The study aim was to evaluate whether mpox vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN) may be associated with viral blips or confirmed virologic failures (CVF) in people with HIV (PWH) receiving antiretroviral therapy and the associated factors.

PWH who received MVA-BN, with HIV-RNA less than 50 copies/ml, and CD4 + lymphocytes at least 200 cells/μl in the 6 months prior to vaccination and at least 1 HIV-RNA determination within 3 months from vaccination.

The primary outcome was occurrence of viral blips (1 HIV-RNA ≥50 copies/ml) and CVF (1 HIV-RNA ≥1000 copies/ml or ≥2 consecutive HIV-RNA ≥50 copies/ml) following MVA-BN. Changes in CD4 + and CD4 + /CD8 + were secondary outcomes. Residual viremia was defined as detectable HIV-RNA less than 50 copies/ml. PWH already vaccinated against smallpox received single-dose MVA-BN. Mann--Whitney rank-sum test or chi-square/Fisher's test applied.

Overall, 187 PWH were included: 147 received two doses of MVA-BN, 40 single-dose. Six viral blips [incidence rate = 1.59/100-person months of follow-up (PMFU), 95% confidence interval (95% CI) = 0.58-3.47], and three CVFs [incidence rate = 0.80/100-PMFU (95% CI = 0.16-2.33)] were observed. Two CVFs occurred at second dose with presence of detectable HIV-RNA following first one, with high compliance to antiretroviral therapy (ART). PWH with viral blips or CVFs had, prior to first vaccination, more frequently residual viremia [77% ( n  = 7) versus 35% ( n  = 62), P  = 0.01]. No differences in ART ( P  = 0.42) and number of MBA-BN doses ( P  = 0.40) was found. In two cases of CVFs, ART was changed; all VBs resolved within 1 month.

Although rare, viral blips and CVFs following MVA-BN vaccination among PWH receiving ART were identified. Close monitoring of HIV-RNA during mpox vaccination should be encouraged.

The largest monkeypox virus (MPXV) outbreak of the 21st century occurred in 2022, which caused epidemics in many countries. According to WHO, physical contact with infected persons, contaminated surfaces, or affected animals might be a source of this virus transmission. A febrile sickness including few symptoms found in MPX disease. Skin rash, lesions, fever, headache, fatigue, and muscle aches symptoms were observed commonly for this disease. Animal and in vitro, studies have shown that the antiviral medications cidofovir and brincidofovir are effective against MPXV. The first-generation vaccinia virus vaccine was developed in 1960, and it helped to protect against MPXV with its side effects. A second-generation vaccination with limitations was launched in 2000. However, the CDC advised vaccinations for risk groups in endemic countries, including positive patients and hospital employees. The JYNNEOS vaccine, administered in 2 doses, also provides protection from MPX. This article presents concisely the most recent findings regarding epidemiology, genomic transmission, signs and symptoms, pathogenesis, diagnosis, and therapeutic interventions for MPXV, which may be helpful to researchers and practitioners. WHO declared that MPX was no longer a global health emergency due to its declining case rate, and a number of countries have reported new incidences. Further research-based investigations must be carried out based on the 2022 outbreak.

The monkeypox virus (MPOX) is an uncommon zoonotic illness brought on by an orthopoxvirus (OPXV). MPOX can occur with symptoms similar to smallpox. Since April 25, 2023, 110 nations have reported 87,113 confirmed cases and 111 fatalities. Moreover, the outspread prevalence of MPOX in Africa and a current outbreak of MPOX in the U.S. have made it clear that naturally occurring zoonotic OPXV infections remain a public health concern. Existing vaccines, though they provide cross-protection to MPOX, are not specific for the causative virus, and their effectiveness in the light of the current multi-country outbreak is still to be verified. Furthermore, as a sequel of the eradication and cessation of smallpox vaccination for four decades, MPOX found a possibility to re-emerge, but with distinct characteristics. The World Health Organization (WHO) suggested that nations use affordable MPOX vaccines within a framework of coordinated clinical effectiveness and safety evaluations. Vaccines administered in the smallpox control program and conferred immunity against MPOX. Currently, vaccines approved by WHO for use against MPOX are replicating (ACAM2000), low replicating (LC16m8), and non-replicating (MVA-BN). Although vaccines are accessible, investigations have demonstrated that smallpox vaccination is approximately 85% efficient in inhibiting MPOX. In addition, developing new vaccine methods against MPOX can help prevent this infection. To recognize the most efficient vaccine, it is essential to assess effects, including reactogenicity, safety, cytotoxicity effect, and vaccine-associated side effects, especially for high-risk and vulnerable people. Recently, several orthopoxvirus vaccines have been produced and are being evaluated. Hence, this review aims to provide an overview of the efforts dedicated to several types of vaccine candidates with different strategies for MPOX, including inactivated, live-attenuated, virus-like particles (VLPs), recombinant protein, nucleic acid, and nanoparticle-based vaccines, which are being developed and launched.

Since the 1970s, human monkeypox (Mpox) has been referred to as a zoonotic endemic disease of specific regions of Africa until early 2022, when a worldwide epidemic outbreak developed. There are many hypotheses on how Mpox could spread to non-endemic regions; the dominant theory is that it spread from the UK and Spain among men who have sex with men (MSM). Therefore, the first clinical case in the Veneto region (Northeast of Italy) was analyzed-which represented a typical case report of the ongoing outbreak-with lesions located mainly in the areas associated with sexual behaviors (genital and oral). This case report highlights the new challenges of Mpox, as it seems to differ from the previous classic manifestation. Indeed, although the patient achieved restitution ad integrum of lesions and complete recovery from the disease, it is deemed necessary to offer communication strategies to involve a heterogeneous audience based on different risks of exposure but without stigmatizing attitudes, avoiding the mistakes made with HIV. The need for broad public involvement is demonstrated by identifying Mpox even in "anomalous cases." Stigma could be an obstacle in engaging patients in proper care and in getting honest answers while contact tracing, as happened in our patient's case; thus, WHO recently renamed monkeypox as Mpox. Abnormal outbreaks in non-endemic countries, with no causal links, must become a warning signal for governments and health policies to design national plans for managing unexpected outbreaks. For an effective public health response, health institutions must communicate effectively, focus on changes and prevention measures, and formulate a plan based on equity and inclusion of the most vulnerable groups.

Recently, there has been an uptick in reported cases of monkeypox (Mpox) in Africa and across the globe. This prompted us to investigate the efficacy of the two vaccines that can prevent Mpox, the modified vaccinia Ankara virus (MVA) vaccine and ACAM2000 vaccine. We analyzed them to determine their rates of humoral cell responses, adverse events, and rash reactions and used these factors as the primary indicators.

This study adapted primary data obtained from the Medline, Google Scholar, and Cochrane Library databases. We included a total of eight studies, three of which explored the ACAM2000 vaccine and five of which explored the JYNNEOS MVA vaccine.

There were significant differences in the rates of humoral responses after inoculation by the two vaccines. JYNNEOS MVA vaccine immunization resulted in a statistically significant increased humoral immune response with an effect size of 81.00 (42.80, 119.21) at a 95% CI and a rash reaction with an effect size of 96.50 (42.09, 235.09.21) at a 95% CI. ACAM2000 resulted in a lesser increase in neutralizing antibodies than JYNNEOS MVA vaccine. Similar findings were identified for the rates of adverse reactions, but the difference was not statistically significant. The differences in rash reaction rates in the two vaccination groups were also not statistically significant.

ACAM2000 and JYNNEOS vaccines have proven to be efficient in preventing Mpox even though variations exist in their modes of action and associated significant effects. The nonreplicating nature of JYNNEOS prevents the occurrence of the adverse effects seen with other vaccines.

Aims of this study were to assess the characteristics of Mpox among people with HIV (PWH) and describe the change of some immune-virological parameters during Mpox virus infection.

Case series of PWH diagnosed with Mpox between May and July 2022 at the Infectious Diseases Unit of San Raffaele Scientific Institute, Milan, Italy.

Real-time PCR was used to detect Mpox virus on oropharyngeal, cutaneous, genital and rectal swabs, plasma, seminal fluids, and urines. The values of the CD4 + lymphocytes and HIV-RNA were assessed both at Mpox diagnosis and after Mpox virological clearance and were compared to those prior to Mpox. The relationship between the symptoms clinical duration of Mpox and the CD4 + cell count at diagnosis was assessed with Spearman's correlation coefficient.

Overall, 28 PWH on antiretroviral therapy with Mpox were evaluated. HIV-RNA did not substantially change at Mpox infection with respect to previous virological profile ( P  = 0.721). However, at time of Mpox diagnosis, we observed a detectable HIV-RNA (196 copies/ml) in one individual previously undetectable (HIV-RNA < 20 copies/ml) and an increase to 1.220 copies/ml in a previously viremic subject (HIV-RNA = 263 copies/ml). No significant differences in CD4 + cell count were found before and at time of Mpox diagnosis ( P  = 0.151) and a higher CD4 + cell count at Mpox diagnosis was marginally related to a lower duration of Mpox symptoms ( r  = -0.341, P  = 0.068).

Among PWH, we advise monitoring HIV viral load at Mpox diagnosis and during follow-up, as well as providing counseling on the results, due to the important individual and community implications.

Monkeypox virus (MPXV) is a double-stranded DNA virus belonging to the Poxviridae family of the genus Orthopoxvirus with two different clades known as West African and Congo Basin. Monkeypox (MPX) is a zoonosis that arises from the MPXV and causes a smallpox-like disease. The endemic disease status of MPX was updated to an outbreak worldwide in 2022. Thus, the condition was declared a global health emergency independent of travel issues, accounting for the primary reason for its prevalence outside Africa. In addition to identified transmission mediators through animal-to-human and human-to-human, especially sexual transmission among men who have sex with men came to prominence in the 2022 global outbreak. Although the severity and prevalence of the disease differ depending on age and gender, some symptoms are commonly observed. Clinical signs such as fever, muscle and headache pain, swollen lymph nodes, and skin rashes in defined body regions are standard and an indicator for the first step of diagnosis. By following the clinical signs, laboratory diagnostic tests like conventional polymerase chain reaction (PCR) or real-time PCR (RT-PCR) are the most common and accurate diagnostic methods. Antiviral drugs such as tecovirimat, cidofovir, and brincidofovir are used for symptomatic treatment. There is no MPXV-specific vaccine; however, currently available vaccines against smallpox enhance the immunization rate. This comprehensive review covers the MPX disease history and the current state of knowledge by assessing broad topics and views related to disease origin, transmission, epidemiology, severity, genome organization and evolution, diagnosis, treatment, and prevention.

Studies of ancient DNA have transformed our understanding of human evolution. Paleogenomics can also reveal historic and prehistoric agents of disease, including endemic, epidemic, and pandemic pathogens. Viruses-and in particular those with single- or double-stranded DNA genomes-are an important part of the paleogenomic revolution, preserving within some remains or environmental samples for tens of thousands of years. The results of these studies capture the public imagination, as well as giving scientists a unique perspective on some of the more slowly evolving viruses which cause disease. In this review, we revisit the first studies of historical virus genetic material in the 1990s, through to the genomic revolution of recent years. We look at how paleogenomics works for viral pathogens, such as the need for careful precautions against modern contamination and robust computational pipelines to identify and analyze authenticated viral sequences. We discuss the insights into virus evolution which have been gained through paleogenomics, concentrating on three DNA viruses in particular: parvovirus B19, herpes simplex virus 1, and smallpox. As we consider recent worldwide transmission of monkeypox and synthetic biology tools that allow the potential reconstruction of extinct viruses, we show that studying historical and ancient virus evolution has never been more topical.

Rapid human-to-human transmission of monkeypox has created a public health emergency requiring prompt, multidisciplinary attention. Dermatologists are at the forefront of diagnosis due to the disease-defining skin lesions. Moreover, patients with pre-existing skin disease and those who are on immunosuppressive medications for skin disease may be at increased risk of severe infection. In this review, a panel of authors with expertise in complex medical dermatology and managing patients on immunosuppression reviews the literature and provides initial guidance for diagnosis and management in dermatology practices. Though there are knowledge gaps due to a lack of controlled studies, we support use of replication-deficit vaccines in all dermatologic patients who meet qualifying risk or exposure criteria. We offer strategies to optimize vaccine efficacy in patients with immunosuppression. We discuss alternative post-exposure treatments and their safety profiles. Finally, we outline supportive care recommendations for cutaneous manifestations of monkeypox. Large scale epidemiologic investigations and clinical trials will ultimately revise and extend our guidance.

Human mpox is an emerging epidemic in the world. The monkey pox virus (MPXV) belongs to the same family of zoonotic Orthopoxviridae as that of the smallpox virus and exhibits similar clinical symptomology. Information regarding its diagnostics, disease epidemiology, surveillance, preventive methods, and treatment strategies are being collated with time. The purpose of this review is to trace the recent events in the scientific platform that have defined new preventive and treatment strategies against mpox. A methodological approach has been used to gather data from the latest literature to comprehensively overview the emerging treatment options. The results portion will cover details regarding the prevention of mpox. It will also shed light on a brief description of contemporary vaccines and antiviral agents that have been evaluated for their treatment potential since the emergence of the mpox threat. These treatment options are setting the pace for controlling the widespread monkeypox infection. However, the limitations attached to these treatment strategies need to be tackled quickly to increase their efficacy so that they can be deployed on a large scale for the prevention of this epidemic becoming another pandemic in this decade.

Monkeypox virus (MPOX) is a zoonotic disease in humans. It is similar genetically to its virus family member, smallpox. This virus has been studied since the 1970s. The virus remains endemic to the Congo and West African regions, but non-endemic spreads have been cited. The most recent non-endemic outbreak in the spring of 2022 amidst the current COVID-19 pandemic is of interest due to its impact on global medical, economic, and societal climates. This literature review aims to highlight the virology, clinical signs and symptoms, diagnosis, prevention, and treatment of MPOX and discuss the social implications of the recent 2022 outbreak. We hope this review can pinpoint important clinical pearls of the MPOX virus and its societal impacts to further promote important discussion of this virus and its disease.

Monkeypox virus is an enveloped DNA virus that belongs to Poxviridae family. The virus is transmitted from rodents to primates via infected body fluids, skin lesions, and respiratory droplets. After being infected with virus, the patients experience fever, myalgia, maculopapular rash, and fluid-filled blisters. It is necessary to differentiate monkeypox virus from other poxviruses during diagnosis which can be appropriately envisioned via DNA analysis from swab samples. During small outbreaks, the virus is treated with therapies administered in other orthopoxviruses infections and does not have its own specific therapy and vaccine. Consequently, in this article, two potential peptides have been designed.

For the purpose of designing a vaccine, protein sequences were retrieved followed by the prediction of B- and T-cell epitopes. Afterward, vaccine structures were predicted which were docked with toll-like receptors. The docked complexes were analyzed with iMODS. Moreover, vaccine constructs nucleotide sequences were optimized and expressed in silico.

COP-B7R vaccine construct (V1) has antigenicity score of 0.5400, instability index of 29.33, z-score of - 2.11-, and 42.11% GC content whereas COP-A44L vaccine construct (V2) has an antigenicity score of 0.7784, instability index of 23.33, z-score of - 0.61, and 48.63% GC content. It was also observed that COP-A44L can be expressed as a soluble protein in Escherichia coli as compared to COP-B7R which requires a different expression system.

The obtained results revealed that both vaccine constructs show satisfactory outcomes after in silico investigation and have significant potential to prevent the monkeypox virus. However, COP-A44L gave better results.

Human monkeypox is a viral zoonotic smallpox-like disease caused by the monkeypox virus (MPXV) and has become the greatest public health threat in the genus Orthopoxvirus after smallpox was eradicated. The host immune response to MPXV plays an essential role in disease pathogenesis and clinical manifestations. MPXV infection leads to skin lesions with the genital area as the main feature in the current outbreak and triggers a strong immune response that results in sepsis, deep tissue abscess, severe respiratory disease, and injuries to multiple immune organs. Emerging evidence shows that the immunopathogenesis of MPXV infection is closely associated with impaired NK-cell function, lymphopenia, immune evasion, increased antibodies, increased blood monocytes and granulocytes, cytokine storm, inhibition of the host complement system, and antibody-dependent enhancement. In this overview, we discuss the immunopathology and immunopathogenesis of monkeypox to aid the development of novel immunotherapeutic strategies against monkeypox.

Monkeypox is a zoonotic disease, presenting with fever, lymphadenopathy and vesicular-pustular skin lesions, that historically has rarely been reported outside the endemic regions of Central and West Africa. It was previously thought that human-to-human transmission was too low to sustain spread. During 2022, the number of cases of monkeypox, caused by clade II, rose rapidly globally, predominantly among men who have sex with men. In previous outbreaks with monkeypox clade 1 in endemic areas, children were disproportionately more affected with higher morbidity and mortality. It is unclear whether children are at similarly higher risk from monkeypox clade II. Nonetheless, children and pregnant women are considered high-risk groups and antiviral treatment should be considered for those affected. While smallpox vaccination offers good protection against monkeypox, the duration of protection is unknown, and infection occurs in vaccinated individuals. Should the current outbreak spread to children, authorities should be prepared to rapidly implement vaccination for children. In this review, we summarize epidemiological and clinical features, as well as the pathogenesis, treatment, and prevention options for monkeypox with a focus on considerations for children.

Infectious threats to humans are continuously emerging. The 2022 worldwide monkeypox outbreak is the latest of these threats with the virus rapidly spreading to 106 countries by the end of September 2022. The burden of the ongoing monkeypox outbreak is manifested by 68,000 cumulative confirmed cases and 26 deaths. Although monkeypox is usually a self-limited disease, patients can suffer from extremely painful skin lesions and complications can occur with reported mortalities. The antigenic similarity between the smallpox virus (variola virus) and monkeypox virus can be utilized to prevent monkeypox using smallpox vaccines; treatment is also based on antivirals initially designed to treat smallpox. However, further studies are needed to fully decipher the immune response to monkeypox virus and the immune evasion mechanisms. In this review we provide an up-to-date discussion of the current state of knowledge regarding monkeypox virus with a special focus on innate immune response, immune evasion mechanisms and vaccination against the virus.

Monkeypox virus is the causative agent of monkeypox disease, belonging to an orthopoxvirus genus, with a disease pattern similar to that of smallpox. The number of monkeypox cases have robustly increased recently in several countries around the world, potentially causing an international threat. Therefore, serious measures are indispensable to be taken to mitigate the spread of the disease and hence, under these circumstances, vaccination is the best choice to neutralize the monkeypox virus. In the current study, we used immunoinformatic approaches to target the L1R, B5R, and A33R proteins of the monkeypox virus to screen for immunogenic cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes to construct multiepitope subunit vaccines. Various online tools predicted the best epitope from immunogenic targets (L1R, B5R, and A33R) of monkeypox virus. The predicted epitopes were joined together by different linkers and subjected to 3D structure prediction. Molecular dynamics simulation analysis confirmed the proper folding of the modeled proteins. The strong binding of the constructed vaccines with human TLR-2 was verified by the molecular docking and determination of dissociation constant values. The GC content and codon adaptation index (CAI) values confirmed the high expression of the constructed vaccines in the pET-28a (+) expression vector. The immune response simulation data delineated that the injected vaccines robustly activated the immune system, triggering the production of high titers of IgG and IgM antibodies. In conclusion, this study provided a solid base of concept to develop dynamic and effective vaccines that contain several monkeypox virus-derived highly antigenic and nonallergenic peptides to control the current pandemic of monkeypox virus.

In the late 1970s, global vaccination programs resulted in the eradication of smallpox. The Monkeypox virus (MPXV), which is closely related to the smallpox-inducing variola virus, was previously endemic only in Sub-Saharan Africa but is currently spreading worldwide. Only older people who have been vaccinated against smallpox are expected to be sufficiently protected against poxviruses. Here I will summarize current knowledge about the virus, the disease caused by MPXV infections, and strategies to limit its spread.