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

• Published in: Nature medicine Vol. 29; no. 1; pp. 270 - 278
• Main Authors: Zaeck, Luca M., Lamers, Mart M., Verstrepen, Babs E., Bestebroer, Theo M., van Royen, Martin E., Götz, Hannelore, Shamier, Marc C., van Leeuwen, Leanne P. M., Schmitz, Katharina S., Alblas, Kimberley, van Efferen, Suzanne, Bogers, Susanne, Scherbeijn, Sandra, Rimmelzwaan, Guus F., van Gorp, Eric C. M., Koopmans, Marion P. G., Haagmans, Bart L., GeurtsvanKessel, Corine H., de Vries, Rory D.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2023; Nature Publishing Group
• Subjects: 631/250/2152/2153/1291; 631/250/590/1867; 692/699/255/2514; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antibody response; At risk populations; Biomedical and Life Sciences; Biomedicine; Cancer Research; Effectiveness; Humans; Immunization; Infectious Diseases; Influenza Vaccines; Metabolic Diseases; Molecular Medicine; Monkeypox virus; Mpox; Mpox (monkeypox); Neurosciences; Neutralizing; Public health; Smallpox; Vaccination; Vaccine efficacy; Vaccines; Vaccinia; Vaccinia virus; Viruses
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-022-02090-w

In July 2022, the ongoing monkeypox (MPX) outbreak was declared a public health emergency of international concern. Modified vaccinia Ankara—Bavarian Nordic (MVA-BN, also known as Imvamune, JYNNEOS or Imvanex) is a third-generation smallpox vaccine that is authorized and in use as a vaccine against MPX. To date, there are no data showing MPX virus (MPXV)-neutralizing antibodies in vaccinated individuals nor vaccine efficacy against MPX. Here we show that MPXV-neutralizing antibodies can be detected after MPXV infection and after historic smallpox vaccination. However, a two-shot MVA-BN immunization series in non-primed individuals yields relatively low levels of MPXV-neutralizing antibodies. Dose-sparing of an MVA-based influenza vaccine leads to lower MPXV-neutralizing antibody levels, whereas a third vaccination with the same MVA-based vaccine significantly boosts the antibody response. As the role of MPXV-neutralizing antibodies as a correlate of protection against disease and transmissibility is currently unclear, we conclude that cohort studies following vaccinated individuals are necessary to assess vaccine efficacy in at-risk populations. Historic smallpox vaccination and monkeypox virus (MPXV) infection elicit MPXV-neutralizing antibodies, but MPXV-neutralizing antibodies are less frequent and of lower magnitude after vaccination with MVA-BN—the vaccine approved and in use for protection against MPXV and smallpox.