The modified vaccinia Ankara-Bavarian Nordic (MVA-BN) smallpox vaccine generates neutralizing antibodies against the emerging clade Ib of the monkeypox virus (MPXV), though at lower levels than against the more prevalent clade IIb, according to new research published in February 2026 in the journal Emerging Infectious Diseases. The findings, from a study conducted by researchers at the University of Liverpool and collaborating institutions in the UK and Nigeria, are particularly relevant given the recent designation of clade Ib as a public health emergency of international concern due to its increased severity and mortality, especially among children.
Mpox, a zoonotic viral disease, has seen shifting dynamics in recent years. While historically endemic to Central and West Africa, a global outbreak in 2022 was driven by the clade IIb strain. More recently, the emergence of clade Ib, first identified in the Democratic Republic of the Congo (DRC) in 2023, has raised concerns. The World Health Organization recommends vaccination with MVA-BN for those at high risk of contracting mpox, but questions remained about the vaccine’s effectiveness against this newer variant. Understanding the immune response to different MPXV clades is crucial for informing public health strategies and potential vaccine adjustments.
Neutralizing Antibody Response to Clade Ib
Researchers recruited 25 healthcare workers in the United Kingdom who had been vaccinated with MVA-BN due to occupational exposure risk. They measured neutralizing antibodies against both clade Ib and clade IIb using a plaque reduction neutralization test (PRNT). A control group of four individuals immunized with the IMOJEV vaccine, another live attenuated vaccine, was also included. The study found that while MVA-BN vaccination did generate neutralizing antibodies against both clades, the levels were significantly lower for clade Ib. The median PRNT50 value – a measure of antibody potency – was 25.9 for clade Ib compared to 44.8 for clade IIb (p = 0.0028).
The study also highlighted the importance of complement in MPXV neutralization. Complement, a part of the immune system, is required for effective virus control in vitro. Researchers found that complement was necessary for neutralizing MPXV in laboratory settings, consistent with previous research. They used non-heat-inactivated serum to accurately measure MPXV neutralization, a method previously described in scientific literature.
Implications for Vaccine Protection
While the MVA-BN vaccine did elicit a measurable immune response against clade Ib, the lower neutralizing antibody titers raise questions about the level of protection conferred. The researchers acknowledge that the clinical relevance of this difference is currently uncertain, as the protective threshold for MPXV neutralizing antibodies remains undefined. Further research, including case-control studies, is needed to establish antibody correlates of protection.
The study’s findings align with previous research demonstrating relatively low levels of MPXV neutralization following MVA-BN vaccination. In the UK, one dose of MVA-BN has been shown to provide short-term protection of 78% against mpox, primarily in men who have sex with men. However, the durability of this protection and whether booster doses are needed to enhance immunity against clade Ib remain open questions. The researchers note that the small sample size of their study is a limitation, but emphasize the relevance of demonstrating neutralization of clade Ib in vaccinated healthcare workers, a high-risk population.
Complement and Neutralization
The study’s exploration of complement’s role in MPXV neutralization adds nuance to understanding the immune response. Researchers observed that foreign complement sources can have nonspecific effects on MPXV neutralization, highlighting the importance of careful experimental design. Guinea pig serum, for example, exhibits neutralization activity against other viruses, like mumps, independent of specific antibodies.
Dr. Victoria Sheridan, a postdoctoral researcher at the University of Liverpool and lead author of the study, focuses her research on virus-host interactions and medical countermeasures. Her work, conducted in the laboratory of Julian Hiscox, contributes to a growing body of knowledge aimed at improving our preparedness for emerging infectious diseases.
The findings underscore the necessitate for continued monitoring of MPXV evolution and ongoing evaluation of vaccine effectiveness against emerging variants. While MVA-BN appears to offer some protection against clade Ib, the lower neutralizing antibody response suggests that further investigation is warranted to optimize vaccination strategies and ensure robust protection against this increasingly concerning strain of mpox. The researchers suggest that assessing the durability of the immune response and exploring the potential benefits of a third vaccine dose are important next steps.
The World Health Organization continues to recommend vaccination for those at high risk of mpox exposure. For the latest information and guidance on mpox, including vaccination recommendations, please visit the WHO website: https://www.who.int/news-room/monkeypox.
Dr. Sheridan is a postdoctoral researcher in the laboratory of Julian Hiscox, University of Liverpool. Her research focuses on virus host interactions and the apply of medical countermeasures.
This research provides valuable insights into the immune response to the evolving monkeypox virus. As the virus continues to circulate and new variants emerge, ongoing research and surveillance will be critical to protecting public health.
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