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ECRAID-Base POS-Disease X

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

The team's findings were published in Nature Medicine.

Published in

  • Nature Medicine


  • Luca M. Zaeck
  • Mart M. Lamers
  • Martin E. van Royen
  • Hannelore Götz
  • Marc C. Shamier
  • Leanne P. M. van Leeuwen
  • Katharina S. Schmitz
  • Kimberley Alblas
  • Suzanne van Efferen
  • Susanne Bogers
  • Sandra Scherbeijn
  • Guus F. Rimmelzwaan
  • Eric C. M. van Gorp
  • Marion P. G. Koopmans
  • Bart L. Haagmans
  • Corine H. GeurtsvanKessel
  • Rory D. de Vries

In May 2022, a multi-country outbreak of monkeypox started affecting Europe and other continents. Ecraid mobilised its network for a rapid clinical research response that included action by the ECRAID-Base project's POS-Disease X team. Their findings on the immunological response to monkeypox infection and vaccination were published in Nature Medicine.


Ecraid began work on monkeypox early in the 2022 outbreak and has been involved with several initiatives tackling the disease. Its clinical research activities are focused on elucidating the viral dynamics during infection, the immunological response to infection and vaccination, and the effects of treatment. Some of these efforts are already paying off. 

A team from the Department of Viroscience at the Erasmus University Medical Center in Rotterdam, the Netherlands, recently published the results of a study on monkeypox-neutralizing antibody levels related to infection and vaccination status. An unedited version of this manuscript appeared in Nature Medicine before official final publication, so as to give the scientific community early access to its important findings.

Modified vaccinia virus Ankara-Bavarian Nordic (MVA-BN, also known as Imvamune, Jynneos, or Imvanex) is a 3rd generation smallpox vaccine that is authorized and in use as a vaccine against monkeypox. To date, however, there is no data demonstrating monkeypoxvirus-neutralizing antibodies in vaccinated individuals, or vaccine efficacy against the virus. The team set out to investigate monkeypox-neutralizing antibodies in cohorts of historic smallpox-vaccinated, monkeypox-infected and recent smallpox-vaccinated individuals, as well as people with a recent MVA-based influenza vaccine (MVA-H5). 

They found that monkeypox-neutralizing antibodies can be detected after infection and after historic smallpox vaccination. However, a 2-shot smallpox immunization series in non-primed individuals yields relatively low levels of monkeypox-neutralizing antibodies. Dose-sparing of an MVA-based influenza vaccine leads to lower monkeypox-neutralizing antibody levels, whereas a third vaccination with the same vaccine significantly boosts the antibody response. 

Corine Geurts van Kessel, clinical virologist and principal investigator, commented:

Our research provides critical insights into whether the currently employed vaccines used to combat the monkeypox outbreak are immunogenic and cross-reactive against the virus in the first place. Moreover, we provide tools for researchers to assess monkeypox-specific immune responses and consequently lay the foundation for more in-depth comprehension of monkeypox-specific immune responses.

As the role of monkeypox-neutralizing antibodies as a correlate of protection against disease and transmissibility is currently unclear, the authors conclude that cohort studies following vaccinated individuals are necessary to assess vaccine efficacy in at-risk populations.

Monkeypox outbreak

Monkeypox is a relatively rare disease. In most patients, it causes a painful rash, and other symptoms in some. Rarely, it can cause complications that can be fatal, with higher case fatality rates among children and young adults, as well as immunocompromised individuals. Since its discovery in the late 1950’s, outbreaks have been occurring in communities in Central and West Africa. However, in early May 2022, a multi-country outbreak of monkeypox started affecting the United Kingdom (UK), Europe, Asia, the Americas, and Australia. Most recognized infections have been in men with high-risk exposure for transmission (men who have sex with men), but while disease transmission outside this population is still rare, there is concern that expansion is possible if the outbreak continues to evolve. 

About POS-Disease X

High-density urban areas are increasingly becoming the hubs for the explosive spread of infectious disease outbreaks. This ECRAID-Base study POS-Disease X focuses on preparing Europe for a ‘Disease X‘ scenario – an unexplained febrile illness with unusual epidemiology and/or clinical presentation and of likely virus etiology. 

The team is also tasked with building and maintaining operational resilience for rapid response to new or re-emerging threats to the health and security of European citizens. They aim to establish preparedness across all of Ecraid’s service areas for a coordinated clinical research response to infectious disease outbreaks and epidemics. 

Efforts are led by virologist Prof. Marion Koopmans who is Head of the Department of Viroscience at the Erasmus University Medical Center.