Recent research highlights the evolving landscape of mpox (formerly known as monkeypox), with a focus on the emergence of new viral strains and the effectiveness of current vaccination strategies. A study conducted by researchers at the University of Liverpool and the University of Oxford, published in , investigated the neutralizing antibody response to different mpox clades following vaccination with the modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine.
Understanding Mpox Clades and the Global Outbreak
Mpox is a zoonotic viral disease caused by the monkeypox virus (MPXV). The virus is divided into two main clades: I and II, with clade II further subdivided into subclades IIa and IIb. A new subclade of clade I, termed clade Ib, emerged in the Democratic Republic of the Congo (DRC) in . While mpox has historically been reported in 11 countries in Africa since the first human case identified in in the DRC, a global outbreak occurred in driven by the clade IIb strain.
The emergence of clade Ib posed a significant public health threat, being designated a public health emergency of international concern in . This was due to its association with increased disease severity and mortality, particularly among children. The World Health Organization (WHO) recommends vaccination, specifically with the MVA-BN smallpox vaccine, for individuals at high risk of contracting mpox, especially during outbreaks.
Neutralizing Antibody Response to Clade Ib and IIb
Previous research has demonstrated that MVA-BN vaccination generates low levels of neutralizing antibodies against clade IIb and clade Ia. A study in the United Kingdom found that one dose of MVA-BN provided short-term protection of 78% against mpox, primarily in men who have sex with men. However, whether vaccination also induces neutralizing antibodies against the newly emerged clade Ib remained unclear.
To address this question, researchers recruited a convenience sample of 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). The study also included four control participants who had received a different live attenuated vaccine, IMOJEV, and three participants with underlying health conditions (multiple sclerosis, psoriasis, or asthma).
Key Findings: Differences in Neutralization Levels
The study found that two doses of MVA-BN generated a greater neutralizing antibody response against clade IIb compared to clade Ib. This difference was statistically significant (p = 0.0028). The median PRNT50 value – a measure of the serum dilution required to reduce virus plaques by 50% – was 25.9 for clade Ib and 44.8 for clade IIb.
Researchers also investigated the role of complement, a component of the immune system, in neutralizing MPXV. They found that complement is required for neutralization of MPXV in vitro, consistent with previous reports. They used non-heat-inactivated serum for the remainder of the experiments to account for this.
The study noted that the difference in neutralizing antibody titers between the two clades is relatively small, and the clinical relevance of this difference remains uncertain. The protective threshold for MPXV neutralizing antibodies is currently undefined, and case-control studies are needed to establish antibody-specific correlates of protection.
Implications for Vaccination Strategies
The findings suggest that vaccination with MVA-BN may confer moderate protection against disease caused by clade Ib, but the level of protection may be lower than that against clade IIb. The study’s authors acknowledge that the relatively small sample size is a limitation. However, the fact that the study cohort comprised healthcare workers – a high-risk group – makes the findings relevant to informing future vaccine rollout policies.
The low levels of neutralization observed, particularly against clade Ib, raise questions about the durability of the immune response and whether a booster dose might be necessary to enhance protection against infection with this clade. Further research is needed to address these questions. The study did not assess the durability of the responses or the potential benefits of a third dose.
As the mpox virus continues to evolve, ongoing surveillance and research are crucial to understanding the effectiveness of current vaccines and to developing strategies to protect vulnerable populations. The emergence of recombinant strains, such as the Ib/IIb recombinant strain detected in the United Kingdom and India, underscores the importance of continued monitoring and adaptation of public health measures. According to the WHO, as of , the overall public health risk assessment remains moderate for men who have sex with men with new or multiple partners and for sex workers, and low for the general population without specific risk factors.
