Smallpox and mpox vaccination gave little neutralising cover against clade Ib

Design

Multicountry observational study; ELISA binding and PRNT50 neutralisation

Population

191 adults across five vaccination and infection cohorts (USA, Brazil, Portugal)

Primary outcome

Cross-clade neutralising and binding antibody responses

Effect

MVA-BN neutralisation responders 3-15%; low clade Ib neutralisation after clade IIb infection

A multicountry observational study measured binding and neutralising antibodies against mpox clades Ia, Ib and IIb across 191 adults in five cohorts: historical Dryvax vaccination, MVA-BN vaccination, both, prior PCR-confirmed clade IIb infection, and unexposed controls.

Vaccinated plasma bound all three clades but neutralised poorly: detectable neutralisation was present in only 3-15% of MVA-BN samples, with somewhat higher responder rates where Dryvax was also given. Prior clade IIb infection produced broad binding but little neutralisation of clade Ib, and A35-targeted antibodies bound clade I antigens less well than clade IIb.

For practice this tempers confidence that existing vaccination or past infection protects against the expanding clade Ib. Neutralising antibody is a correlate, not the whole of protection, so this is a caution rather than proof that vaccinated people are unprotected; it strengthens the case for clade-aware vaccines and countermeasures.

• Vaccinated plasma bound all mpox clades but neutralised them weakly.
• Detectable neutralisation was present in only 3-15% of MVA-BN samples.
• Prior clade IIb infection gave broad binding but little clade Ib neutralisation.
• Do not assume past mpox vaccination or infection fully covers clade Ib.
• Findings support developing clade-aware vaccines and antibody countermeasures.

Why it matters

It questions the assumption that existing orthopoxvirus immunity carries over to the emerging mpox clade.

Don't overread it

This is observational and measures antibodies only; cellular immunity and real-world vaccine effectiveness are not captured.

The statistics, in plain English

Neutralising antibody is one correlate of protection, not the full picture; low neutralisation titres suggest weaker humoral defence but do not by themselves prove clinical susceptibility.

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