- Design
- Open-label, uncontrolled, dose-escalation, first-in-human phase 1 trial
- Population
- 64 healthy adults (48 vaccinia-naive, 16 vaccinia-experienced)
- Primary outcome
- Solicited reactions within 7 days and adverse events within 28 days
- Effect
- Binding antibody seroresponse 100% after dose 2; clade IIb neutralising antibodies in 62%, 71% and 92% of naive participants at 10, 30 and 60 micrograms; titres waned by 12 months
This first-in-human phase 1 trial gave two intramuscular doses of the quadrivalent mRNA mpox vaccine candidate BNT166a, four weeks apart, to 64 healthy adults: 48 with no previous smallpox or mpox vaccination at 10, 30 or 60 micrograms, and 16 with prior smallpox vaccination at 30 micrograms. It was open label, uncontrolled and non-randomised.
Reactogenicity rose with dose and with the second dose. After dose two, local reactions occurred in 60% (10 micrograms), 86% (30) and 93% (60) of unexposed participants. Most events were mild to moderate. Two participants in the highest-dose group had systemic events of grade 3 or worse, and related adverse events within 28 days occurred in 28%. Binding antibodies to all four antigens appeared in every participant. Neutralising antibodies against clade IIb were found in 62%, 71% and 92% of unexposed participants by dose, and in 93% of those previously vaccinated, and titres fell towards baseline by 12 months.
No efficacy was measured, and neutralising titres are not an established correlate of protection. The trial was published in June 2026 and the candidate has moved to phase 2. It is not available for clinical use.
- Do not expect this vaccine to be available; it is investigational.
- Continue to offer currently recommended mpox vaccination to people at risk, following local policy.
- Counsel about reactogenicity if participants ask about trials of mRNA mpox vaccines.
- Watch for phase 2 data on efficacy, durability and the need for boosters.
Why it matters
It shows that an mRNA approach can produce an antibody response to mpox, while durability is the open question.
Don't overread it
A small, uncontrolled phase 1 study of immune response and safety; it shows nothing about protection against infection.
The statistics, in plain English
Seroresponse of 100% means every participant made binding antibodies, but binding antibodies are not the same as protection. Neutralising antibody rates differed by dose, with small groups of 12 to 14 per arm, so comparisons between doses are imprecise.
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