Novel Monkeypox Clade Raises Concerns About Vaccine Effectiveness

A newly emerged clade of monkeypox virus, designated clade Ib, is prompting investigation into the effectiveness of current vaccines. Recent research indicates that the modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine, while providing protection, may generate lower levels of neutralizing antibodies against clade Ib compared to clade IIb.

Emergence of Clade Ib and Public Health Implications

Monkeypox virus (MPXV) is divided into two main clades: I and II, with clade II further subdivided into subclades IIa and IIb. In 2023, clade Ib emerged in the Democratic Republic of the Congo (DRC) and was designated a public health emergency of international concern in August 2024 due to its association with increased disease severity and mortality, particularly among children .

Study Findings on Antibody Neutralization

Researchers at the Liverpool School of Tropical Medicine, in collaboration with institutions in the UK and Nigeria, investigated the neutralizing antibody response to MVA-BN vaccination against both clade Ib and clade IIb . A study involving 25 healthcare workers vaccinated with MVA-BN revealed that the median neutralizing antibody titer was lower for clade Ib (25.9) than for clade IIb (44.8). This difference was statistically significant (p = 0.0028) .

The study also highlighted the importance of complement in neutralizing MPXV, confirming previous research that complement is required for effective neutralization in vitro .

Implications for Vaccination Strategies

While MVA-BN vaccination does induce some level of neutralization against clade Ib, the lower titers raise questions about the durability and extent of protection. The protective threshold for MPXV neutralizing antibodies remains undefined, necessitating further research, including case-control studies to identify antibody correlates of protection. Given the higher risk of exposure among healthcare workers, evidence of vaccine-associated neutralization is crucial for informing future vaccine rollout policies.

Ongoing Research and Future Directions

The study’s findings suggest that a third dose of MVA-BN may be required to enhance protection against clade Ib infections. Further research is needed to determine the optimal vaccination schedule and to assess the long-term effectiveness of the vaccine against this emerging clade. The Pandemic Preparedness and Response Facility at the University of Liverpool is actively involved in driving advancements in vaccines and therapeutics for potential pandemic threats , and the Royal Liverpool University Hospital hosts a specialist infectious disease unit contributing to this research .