Evaluation of Monkeypox- and Vaccinia virus-neutralizing antibodies in human serum samples after vaccination and natural infection

Introduction In early to mid-2022, an unexpected outbreak of Monkeypox virus infections occurred outside the African endemic regions. Vaccines originally developed in the past to protect against smallpox are one of the available countermeasures to prevent and protect against Orthopoxvirus infections. To date, there are few studies on the cross-reactivity of neutralizing antibodies elicited by previous vaccinia virus-based vaccination and/or Monkeypox virus infection. The aim of this study was to evaluate a possible approach to performing Monkeypox and vaccinia live-virus microneutralization assays in which the read-out is based on the production of cytopathic effect in the cell monolayer. Methods Given the complexity of Orthopoxviruses, the microneutralization assay was performed in such a way as to uncover a potential role of complement, with and without the addition of an external source of Baby Rabbit Complement. A set of human serum samples from individuals who had been naturally infected with Monkeypox virus and individuals who may have and not have undergone vaccinia virus vaccinations, was used to evaluate the performance, sensitivity, and specificity of the assay. Results and conclusions The results of the present study confirm the presence and cross-reactivity of antibodies elicited by vaccinia-based vaccines, which proved able to neutralize the Monkeypox virus in the presence of an external source of complement.

[1]  WHO recommends new name for monkeypox disease. , 2022, Saudi medical journal.

[2]  Z. Butt,et al.  Monkeypox: A Mini-Review on the Globally Emerging Orthopoxvirus , 2022, International journal of environmental research and public health.

[3]  A. Saghazadeh,et al.  Poxviruses and the immune system: Implications for monkeypox virus , 2022, International immunopharmacology.

[4]  W. Schaffner,et al.  Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2022 , 2022, MMWR. Morbidity and mortality weekly report.

[5]  Syed Faraz Ahmed,et al.  Vaccinia-Virus-Based Vaccines Are Expected to Elicit Highly Cross-Reactive Immunity to the 2022 Monkeypox Virus , 2022, Viruses.

[6]  M. Koopmans,et al.  Low levels of monkeypox virus-neutralizing antibodies after MVA-BN vaccination in healthy individuals , 2022, Nature Medicine.

[7]  J. Dordick,et al.  Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance , 2022, Molecules.

[8]  J. Heeney,et al.  Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study , 2022, Journal of Infection.

[9]  C. Wenham,et al.  Monkeypox as a PHEIC: implications for global health governance , 2022, The Lancet.

[10]  J. Shamblin,et al.  Effect of Monkeypox Virus Preparation on the Lethality of the Intravenous Cynomolgus Macaque Model , 2022, Viruses.

[11]  Y. Xiang,et al.  Monkeypox virus emerges from the shadow of its more infamous cousin: family biology matters , 2022, Emerging microbes & infections.

[12]  H. Gendelman,et al.  The 2022 outbreak and the pathobiology of the monkeypox virus , 2022, Journal of autoimmunity.

[13]  B. Bell,et al.  Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022 , 2022, MMWR. Morbidity and mortality weekly report.

[14]  M. Davenport,et al.  Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection , 2021, Nature Medicine.

[15]  A. Manenti,et al.  The theory and practice of the viral dose in neutralization assay: Insights on SARS-CoV-2 “doublethink” effect , 2020, bioRxiv.

[16]  A. Manenti,et al.  Comparative analyses of SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibodies from human serum samples , 2020, bioRxiv.

[17]  A. Manenti,et al.  Evaluation of SARS‐CoV‐2 neutralizing antibodies using a CPE‐based colorimetric live virus micro‐neutralization assay in human serum samples , 2020, Journal of medical virology.

[18]  J. Dunning,et al.  Human-to-Human Transmission of Monkeypox Virus, United Kingdom, October 2018 , 2020, Emerging infectious diseases.

[19]  Rebecca K. Lane,et al.  Poxvirus , 2020, Reference Module in Biomedical Sciences.

[20]  Marc Van Ranst,et al.  Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans , 2018, Front. Public Health.

[21]  Y. Nakazawa,et al.  Emergence of Monkeypox — West and Central Africa, 1970–2017 , 2018, MMWR. Morbidity and mortality weekly report.

[22]  R. Eisenberg,et al.  Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections , 2016, Cell.

[23]  I. Damon,et al.  A highly specific monoclonal antibody against monkeypox virus detects the heparin binding domain of A27 , 2014, Virology.

[24]  S. Hill,et al.  Implications for global health governance. , 2014, Addiction.

[25]  B. Moss Poxvirus DNA replication. , 2013, Cold Spring Harbor perspectives in biology.

[26]  I. Damon Status of human monkeypox: clinical disease, epidemiology and research. , 2011, Vaccine.

[27]  C. Deal,et al.  Utilization of serologic assays to support efficacy of vaccines in nonclinical and clinical trials: meeting at the crossroads. , 2010, Vaccine.

[28]  K. B. Petersen,et al.  A POX‐LIKE DISEASE IN CYNOMOLGUS MONKEYS , 2009 .

[29]  M. R. Benhnia,et al.  Vaccinia Virus Extracellular Enveloped Virion Neutralization In Vitro and Protection In Vivo Depend on Complement , 2008, Journal of Virology.

[30]  Christiana N. Fogg,et al.  Synergistic neutralizing activities of antibodies to outer membrane proteins of the two infectious forms of vaccinia virus in the presence of complement. , 2004, Virology.

[31]  J. Guarner,et al.  Monkeypox Transmission and Pathogenesis in Prairie Dogs , 2004, Emerging infectious diseases.

[32]  J. P. Davis,et al.  The detection of monkeypox in humans in the Western Hemisphere. , 2004, The New England journal of medicine.

[33]  S. Hansen,et al.  Duration of antiviral immunity after smallpox vaccination , 2003, Nature Medicine.

[34]  E. A. Uvarova,et al.  Human monkeypox and smallpox viruses: genomic comparison , 2001, FEBS letters.

[35]  M. Law,et al.  Antibody neutralization of the extracellular enveloped form of vaccinia virus. , 2001, Virology.

[36]  Geoffrey L. Smith,et al.  Intracellular and extracellular vaccinia virions enter cells by different mechanisms. , 1998, The Journal of general virology.

[37]  D. Thomas,et al.  A prospective study of serum antibody and protection against smallpox. , 1972, The American journal of tropical medicine and hygiene.

[38]  J. R. Scotti,et al.  Available From , 1973 .

[39]  A. Hussong,et al.  Meeting at the Crossroads. , 1993 .