US study reports efficacy of single- vs double-dose mpox vaccine as 36% vs 66%
18 May 2023. Related: Early access, mpox (monkeypox).
Simon Collins, HIV i-Base
There is limited direct data available to estimate the efficacy of the mpox vaccine used last year (Imvanex, Imvamune, Jynneos, MVA) – and, for ethical reasons, none from prospective randomised controlled studies.
In addition, recent estimates from observational studies are flawed by not adjusting for demographic and other factors associated with both risk and likely access to vaccines.
A large case-control study published in the NEJM is therefore important for having a closer match between participants in the case and control groups, including for markers associated with health-seeking behaviour and for calendar time. 
The study used data from a large electronic database (>170 million records) to identify 2266 cases (diagnosed with mpox) who were matched (at least 1:4) to two control groups: (i) 4033 people recently diagnosed with HIV, and (ii) 20,570 HIV negative men actively receiving PrEP. All criteria related to a three-month period from mid-August to mid-November 2022.
Most importantly, the study adjusted for vaccination status, age group, ethnicity, social vulnerability index and presence or absence of HIV-related complications. It also reported results that showed significantly lower efficacy rates compared to previous studies and significantly lower levels of protection after only one dose of the vaccine.
Overall 25/2193 cases and 335/8319 controls received two doses (full vaccination). This produced an adjusted vaccine efficacy of 66.0% (95%CI: 47.4 to 78.1). In the 146 cases and 1000 controls who received only one vaccine dose, estimated efficacy dropped to 35.8% (95% CI: 22.1 to 47.1).
Although several observational studies have reported high levels of protection (>85%), including from the US, UK and Israel, these results have not been adjusted for the demographic and behavioural differences between groups who received the vaccine vs those who didn’t, even though these differences have been widely acknowledged. [2, 3]
Vaccinations were disproportionally accessed by largely white cis gay men who were already connected to social media networks used to publicise vaccine programmes. These people were often at lower or even negligible risk from mpox, and in whom mpox cases would be expected to be significantly lower.
Other challenges in estimating mpox vaccine efficacy include:
- Case numbers of mpox were already dropping before vaccines were widely available, certainly in the UK.
- Uncertainty over the time needed between having a vaccine shot and developing an immune response (likely at least two weeks).
- Continued behaviour changes to reduce risk, so that people actively seeking vaccines might also continue to cautiously avoid risk until at least two weeks after the second dose (if available) and possibly for much longer.
The results from the current paper by Deputy et al are therefore welcomed as a more reliable base to estimate population risk from future outbreaks of mpox.
Recent modelling by the US CDC calculated that at least 33% of the at-risk population need to have full vaccine cover in order to prevent an outbreak similar to that in 2022. 
Currently, only around 26,000 gay and bisexual men in the UK at highest risk have received two vaccines. 
STOP PRESS: As this report was published, a second US case-control study was published by MMWR reporting higher levels of vaccine efficacy. The results from will be reviewed shortly so both studies can be considered together. Both studies emphasise the importance of completing the two-dose course of injections. 
- Deputy NP et al. Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States. NEJM. (18 May 2023).
- Payne AB et al. Incidence of monkeypox among unvaccinated persons compared with persons receiving ≥1 JYNNEOS vaccine dose—32 US Jurisdictions July 31–September 3 2022. MMWR Morb Mortal Wkly Rep 2022 71: 1278–82.
- Bertran M et al. Effectiveness of one dose of MVA-BN smallpox vaccine against mpox in England using the case- coverage method: an observational study. Lancet Infect Dis 2023. (13 March 2023).
- Daskalakis D. 18th EACS/ECDC webinar. (2 May 2023).
- UKHSA press release. People still eligible for mpox vaccine urged to come forward. (22 March 2023).
- Rosenberg ES et al. Effectiveness of JYNNEOS Vaccine Against Diagnosed Mpox Infection — New York, 2022. MMWR Morb Mortal Wkly Rep 2023;72:559–563. (18 May 2023).