1
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Vilibic-Cavlek T, Bogdanic M, Savic V, Hruskar Z, Barbic L, Stevanovic V, Antolasic L, Milasincic L, Sabadi D, Miletic G, Coric I, Mrzljak A, Listes E, Savini G. Diagnosis of West Nile virus infections: Evaluation of different laboratory methods. World J Virol 2024; 13:95986. [PMID: 39722752 PMCID: PMC11551685 DOI: 10.5501/wjv.v13.i4.95986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 08/14/2024] [Accepted: 08/27/2024] [Indexed: 10/18/2024] Open
Abstract
BACKGROUND The diagnosis of West Nile virus (WNV) is challenging due to short-term and low-level viremia, flavivirus cross-reactivity, and long immunoglobulin M (IgM) persistence. AIM To evaluate different methods for WNV detection [reverse transcription-polymerase chain reaction (RT-PCR), IgM/IgG antibodies, IgG avidity] in serum, cerebrospinal fluid (CSF), and urine samples of patients with confirmed WNV infection. METHODS The study included patients with confirmed WNV neuroinvasive infection (n = 62), asymptomatic WNV seropositive individuals (n = 22), and individuals with false-positive WNV IgM antibodies (n = 30). WNV RNA was detected using RT-PCR. A commercial ELISA was used to detect WNV IgM/IgG antibodies with confirmation of cross-reactive samples using a virus neutralization test (VNT). IgG-positive samples were tested for IgG avidity. RESULTS The WNV-RNA detection rates were significantly higher in the urine (54.5%)/serum (46.4%) than in CSF (32.2%). According to the sampling time, the WNV-RNA detection rates in urine collected within 7 days/8-14/≥ 15 days were 29.4/66.6/62.5% (P = 0.042). However, these differences were not observed in the CSF. The median RT-PCR cycle threshold values were significantly lower in urine (32.5, IQR = 28-34) than in CSF (34.5, IQR = 33-36). The frequency of positive WNV IgM and IgG significantly differed according to the sampling time in serum but not in CSF. Positive IgM/IgG antibodies were detected in 84.3/9.3% of serum samples collected within 7 days, 100/71.1% of samples collected 8-14, and 100% samples collected after ≥ 15 days. Recent WNV infection was confirmed by low/borderline avidity index (AI) in 13.6% of asymptomatic individuals. A correlation between ELISA and AI was strong negative for IgM and strong positive for IgG. No significant correlation between ELISA IgG and VNT was found. CONCLUSION The frequency of WNV RNA and antibody detection depends on the sampling time and type of clinical samples. IgG avidity could differentiate recent WNV infections from long-persisting IgM antibodies.
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Affiliation(s)
- Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, Zagreb 10000, Croatia
| | - Zeljka Hruskar
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Ljiljana Antolasic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Ljiljana Milasincic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Dario Sabadi
- Department of Infectious Diseases, Clinical Hospital Center Osijek, Osijek 31000, Croatia
- Medical Faculty, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
| | - Gorana Miletic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Ivona Coric
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Eddy Listes
- Croatian Veterinary Institute, Veterinary Institute Split, Split 21000, Croatia
| | - Giovanni Savini
- OIE Reference Center for West Nile Disease, Istituto Zooprofilattico Sperimentale, G. Caporale, Teramo 64100, Italy
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2
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Wilks SH, Mühlemann B, Shen X, Türeli S, LeGresley EB, Netzl A, Caniza MA, Chacaltana-Huarcaya JN, Corman VM, Daniell X, Datto MB, Dawood FS, Denny TN, Drosten C, Fouchier RAM, Garcia PJ, Halfmann PJ, Jassem A, Jeworowski LM, Jones TC, Kawaoka Y, Krammer F, McDanal C, Pajon R, Simon V, Stockwell MS, Tang H, van Bakel H, Veguilla V, Webby R, Montefiori DC, Smith DJ. Mapping SARS-CoV-2 antigenic relationships and serological responses. Science 2023; 382:eadj0070. [PMID: 37797027 PMCID: PMC12145880 DOI: 10.1126/science.adj0070] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 08/23/2023] [Indexed: 10/07/2023]
Abstract
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns of cross-reactivity among 21 variants and 15 groups of human sera obtained after primary infection with 10 different variants or after messenger RNA (mRNA)-1273 or mRNA-1273.351 vaccination. We found antigenic differences among pre-Omicron variants caused by substitutions at spike-protein positions 417, 452, 484, and 501. Quantifying changes in response breadth over time and with additional vaccine doses, our results show the largest increase between 4 weeks and >3 months after a second dose. We found changes in immunodominance of different spike regions, depending on the variant an individual was first exposed to, with implications for variant risk assessment and vaccine-strain selection.
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Affiliation(s)
- Samuel H Wilks
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK
| | - Barbara Mühlemann
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
| | - Xiaoying Shen
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
| | - Sina Türeli
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK
| | - Eric B LeGresley
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK
| | - Antonia Netzl
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK
| | - Miguela A Caniza
- Department of Global Pediatric Medicine, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA
| | | | - Victor M Corman
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
| | - Xiaoju Daniell
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Michael B Datto
- Department of Pathology, Duke University School of Medicine, Durham, NC, USA
| | | | - Thomas N Denny
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
| | - Christian Drosten
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
| | | | - Patricia J Garcia
- School of Public Health, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Peter J Halfmann
- Influenza Research Institute, Department of Pathobiological Science, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
| | - Agatha Jassem
- BC Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Lara M Jeworowski
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
| | - Terry C Jones
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
| | - Yoshihiro Kawaoka
- Influenza Research Institute, Department of Pathobiological Science, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
- Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), University of Tokyo, Tokyo, Japan
| | - Florian Krammer
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Pathology, Cellular and Molecular Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Charlene McDanal
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | | | - Viviana Simon
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Pathology, Cellular and Molecular Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- The Global Health and Emerging Pathogen Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Melissa S Stockwell
- Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, and Department of Population and Family Health, Mailman School of Public Health, New York, NY, USA
| | - Haili Tang
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Harm van Bakel
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Vic Veguilla
- Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Richard Webby
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - David C Montefiori
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
| | - Derek J Smith
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK
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3
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Astakhova EA, Morozov AA, Byazrova MG, Sukhova MM, Mikhailov AA, Minnegalieva AR, Gorchakov AA, Filatov AV. Antigenic Cartography Indicates That the Omicron BA.1 and BA.4/BA.5 Variants Remain Antigenically Distant to Ancestral SARS-CoV-2 after Sputnik V Vaccination Followed by Homologous (Sputnik V) or Heterologous (Comirnaty) Revaccination. Int J Mol Sci 2023; 24:10493. [PMID: 37445671 PMCID: PMC10341525 DOI: 10.3390/ijms241310493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
The rapid emergence of evasive SARS-CoV-2 variants is an ongoing challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform of the sufficiency of the breadth of the antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received the Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. A traditional analysis of neutralization titers against the WT (wild-type), Alpha, Beta, Delta, Omicron BA.1, and BA.4/BA.5 variants showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all of the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from the WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.
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Affiliation(s)
- Ekaterina A. Astakhova
- Laboratory of Immunochemistry, National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, 115522 Moscow, Russia
- Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
| | - Alexey A. Morozov
- Laboratory of Immunochemistry, National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, 115522 Moscow, Russia
- Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
| | - Maria G. Byazrova
- Laboratory of Immunochemistry, National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, 115522 Moscow, Russia
- Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
- Ministry of Science and Higher Education of Russia, RUDN University, 117198 Moscow, Russia
| | - Maria M. Sukhova
- Laboratory of Immunochemistry, National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, 115522 Moscow, Russia
- Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
| | - Artem A. Mikhailov
- Laboratory of Immunochemistry, National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, 115522 Moscow, Russia
- Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
| | - Aygul R. Minnegalieva
- Laboratory of Synthetic and Evolutionary Biology, Okinawa Institute of Science and Technology, Okinawa 904-0495, Japan
| | - Andrey A. Gorchakov
- Laboratory of Immunogenetics, Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
| | - Alexander V. Filatov
- Laboratory of Immunochemistry, National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, 115522 Moscow, Russia
- Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
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4
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Wilks SH, Mühlemann B, Shen X, Türeli S, LeGresley EB, Netzl A, Caniza MA, Chacaltana-Huarcaya JN, Corman VM, Daniell X, Datto MB, Dawood FS, Denny TN, Drosten C, Fouchier RAM, Garcia PJ, Halfmann PJ, Jassem A, Jeworowski LM, Jones TC, Kawaoka Y, Krammer F, McDanal C, Pajon R, Simon V, Stockwell MS, Tang H, van Bakel H, Veguilla V, Webby R, Montefiori DC, Smith DJ. Mapping SARS-CoV-2 antigenic relationships and serological responses. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2022.01.28.477987. [PMID: 35860221 PMCID: PMC9298128 DOI: 10.1101/2022.01.28.477987] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
During the SARS-CoV-2 pandemic, multiple variants escaping pre-existing immunity emerged, causing concerns about continued protection. Here, we use antigenic cartography to analyze patterns of cross-reactivity among a panel of 21 variants and 15 groups of human sera obtained following primary infection with 10 different variants or after mRNA-1273 or mRNA-1273.351 vaccination. We find antigenic differences among pre-Omicron variants caused by substitutions at spike protein positions 417, 452, 484, and 501. Quantifying changes in response breadth over time and with additional vaccine doses, our results show the largest increase between 4 weeks and >3 months post-2nd dose. We find changes in immunodominance of different spike regions depending on the variant an individual was first exposed to, with implications for variant risk assessment and vaccine strain selection.
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Affiliation(s)
- Samuel H Wilks
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
| | - Barbara Mühlemann
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
| | - Xiaoying Shen
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
| | - Sina Türeli
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
| | - Eric B LeGresley
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
| | - Antonia Netzl
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
| | - Miguela A Caniza
- Department of Global Pediatric Medicine, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA
| | | | - Victor M Corman
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
| | - Xiaoju Daniell
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Michael B Datto
- Department of Pathology, Duke University School of Medicine, Durham, NC, USA
| | | | - Thomas N Denny
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
| | - Christian Drosten
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
| | | | - Patricia J Garcia
- School of Public Health, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Peter J Halfmann
- Influenza Research Institute, Department of Pathobiological Science, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
| | - Agatha Jassem
- BC Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Lara M Jeworowski
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
| | - Terry C Jones
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
| | - Yoshihiro Kawaoka
- Influenza Research Institute, Department of Pathobiological Science, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
- Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), University of Tokyo, Tokyo, Japan
| | - Florian Krammer
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Pathology, Cellular and Molecular Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Charlene McDanal
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | | | - Viviana Simon
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Pathology, Cellular and Molecular Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- The Global Health and Emerging Pathogen Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Melissa S Stockwell
- Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, and Department of Population and Family Health, Mailman School of Public Health, New York, NY, USA
| | - Haili Tang
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Harm van Bakel
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Vic Veguilla
- Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Richard Webby
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - David C Montefiori
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
| | - Derek J Smith
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
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5
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Jurisic L, Malatesta D, Zaccaria G, Di Teodoro G, Bonfini B, Valleriani F, Teodori L, Bencivenga F, Leone A, Ripà P, D'Innocenzo V, Rossi E, Lorusso A. Immunization with Usutu virus and with a chimeric West Nile virus (WNV) harboring Usutu-E protein protects immunocompetent adult mice against lethal challenges with different WNV lineage 1 and 2 strains. Vet Microbiol 2023; 277:109636. [PMID: 36580873 DOI: 10.1016/j.vetmic.2022.109636] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 12/09/2022] [Accepted: 12/11/2022] [Indexed: 12/15/2022]
Abstract
West Nile virus (WNV) and Usutu virus (USUV), two antigenically related flaviviruses co-circulating in Europe, can cause severe neurological disease in animals and humans. The immune response against USUV and WNV and their immunopathogenesis are still poorly investigated. Here we present results upon sequential infections of adult immunocompetent CD-1 and BALB/c mice primed with two different doses (high dose, HD or low dose, LD) of an USUV isolate and challenged with HD or LD of three different WNV isolates. CD-1 and BALB/c LD USUV-primed mice, regardless of the dose, are largely protected from lethal WNV challenges despite showing no detectable neutralizing antibodies. Furthermore, mice immunized with a chimeric virus harboring the E protein of USUV within the WNV backbone (WNVE-USUV) are protected against a lethal challenge with WNV. We believe these findings could contribute to understanding the dynamics of the interaction during sequential infection of these two flaviviruses.
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Affiliation(s)
- Lucija Jurisic
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy; Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy
| | - Daniela Malatesta
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Guendalina Zaccaria
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Giovanni Di Teodoro
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Barbara Bonfini
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Fabrizia Valleriani
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Liana Teodori
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | | | - Alessandra Leone
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Paola Ripà
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Vincenzo D'Innocenzo
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Emanuela Rossi
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy
| | - Alessio Lorusso
- Istituto Zooprofilattico Sperimentale Teramo (IZS-Te), Campo Boario, Teramo, Italy.
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6
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Hou B, Chen H, Gao N, An J. Cross-Reactive Immunity among Five Medically Important Mosquito-Borne Flaviviruses Related to Human Diseases. Viruses 2022; 14:1213. [PMID: 35746683 PMCID: PMC9228836 DOI: 10.3390/v14061213] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 05/28/2022] [Accepted: 05/29/2022] [Indexed: 02/04/2023] Open
Abstract
Flaviviruses cause a spectrum of potentially severe diseases. Most flaviviruses are transmitted by mosquitoes or ticks and are widely distributed all over the world. Among them, several mosquito-borne flaviviruses are co-epidemic, and the similarity of their antigenicity creates abundant cross-reactive immune responses which complicate their prevention and control. At present, only effective vaccines against yellow fever and Japanese encephalitis have been used clinically, while the optimal vaccines against other flavivirus diseases are still under development. The antibody-dependent enhancement generated by cross-reactive immune responses against different serotypes of dengue virus makes the development of the dengue fever vaccine a bottleneck. It has been proposed that the cross-reactive immunity elicited by prior infection of mosquito-borne flavivirus could also affect the outcome of the subsequent infection of heterologous flavivirus. In this review, we focused on five medically important flaviviruses, and rearranged and recapitulated their cross-reactive immunity in detail from the perspectives of serological experiments in vitro, animal experiments in vivo, and human cohort studies. We look forward to providing references and new insights for the research of flavivirus vaccines and specific prevention.
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Affiliation(s)
- Baohua Hou
- Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; (B.H.); (J.A.)
| | - Hui Chen
- Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; (B.H.); (J.A.)
- Experimental Center for Basic Medical Teaching, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
| | - Na Gao
- Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; (B.H.); (J.A.)
| | - Jing An
- Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; (B.H.); (J.A.)
- Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100093, China
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Zaccaria G, Malatesta D, Jurisic L, Marcacci M, Di Teodoro G, Conte A, Teodori L, Monaco F, Marini V, Casaccia C, Savini G, Di Gennaro A, Rossi E, D'Innocenzo V, D'Alterio N, Lorusso A. The envelope protein of Usutu virus attenuates West Nile virus virulence in immunocompetent mice. Vet Microbiol 2021; 263:109262. [PMID: 34715462 DOI: 10.1016/j.vetmic.2021.109262] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 10/17/2021] [Indexed: 11/28/2022]
Abstract
West Nile virus (WNV) and Usutu virus (USUV) are the two most widespread mosquito-borne flaviviruses in Europe causing severe neuroinvasive disease in humans. Here, following standardization of the murine model with wild type (wt) viruses, we engineered WNV and USUV genome by reverse genetics. A recombinant virus carrying the 5' UTR of WNV within the USUV genome backbone (r-USUV5'-UTR WNV) was rescued; when administered to mice this virus did not cause signs or disease as wt USUV suggesting that 5' UTR of a marked neurotropic parental WNV was not per se a virulence factor. Interestingly, a chimeric virus carrying the envelope (E) protein of USUV in the WNV genome backbone (r-WNVE-USUV) showed an attenuated profile in mice compared to wt WNV but significantly more virulent than wt USUV. Moreover, except when tested against serum samples originating from a live WNV infection, r-WNVE-USUV showed an identical antigenic profile to wt USUV confirming that E is also the major immunodominant protein of USUV.
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Affiliation(s)
- Guendalina Zaccaria
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Daniela Malatesta
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Lucija Jurisic
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy; Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy
| | - Maurilia Marcacci
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy; Dipartimento di Medicina Veterinaria, University of Bari, Valenzano, Bari, Italy
| | - Giovanni Di Teodoro
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Annamaria Conte
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Liana Teodori
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Federica Monaco
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Valeria Marini
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Claudia Casaccia
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Giovanni Savini
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Annapia Di Gennaro
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Emanuela Rossi
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Vincenzo D'Innocenzo
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Nicola D'Alterio
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy
| | - Alessio Lorusso
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise (IZSAM), Campo Boario, 64100 Teramo, Italy.
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