Low levels of monkeypox virus neutralizing antibodies after MVA-BN vaccination in healthy individuals

Abstract

Abstract In July 2022, the ongoing monkeypox (MPX) outbreak was declared a public health emergency of international concern by the World Health Organization. Modified vaccinia virus Ankara (MVA-BN, also known as Imvamune, Jynneos, or Imvanex) is a 3 rd generation smallpox vaccine that was generated by serial passaging of the more pathogenic parental vaccinia virus (VACV), and is authorized as a vaccine against MPX in humans in a two-shot regimen. Up to now, there is a lack of data that demonstrate MPX virus (MPXV)-neutralizing antibodies in vaccinated individuals and vaccine efficacy data against MPXV infection. Here, we measure MVA-, VACV-, and MPXV-reactive binding and neutralizing antibodies with validated in-house assays in cohorts of historically smallpox-vaccinated, MPXV PCR-positive, and recently MVA-BN-vaccinated individuals. We show that MPXV neutralizing antibodies were detected across all cohorts in individuals with MPXV exposure as well as those who received historic (VACV) vaccination. However, a primary MVA-BN immunization series in non-primed individuals yields relatively low levels of MPXV neutralizing antibodies. As the role of MPXV neutralizing antibodies for protection against disease and transmissibility is currently unclear and no correlate of protection against MPXV infection has been identified yet, this raises the question how well vaccinated individuals are protected. Dose-sparing leads to lower antibody levels, whereas a third MVA vaccination further boosts the antibody response. Cohort studies following vaccinated individuals are necessary to further assess vaccine efficacy in risk populations and determine correlates of protection for this emerging pathogen.