UK data on efficacy of mpox vaccine: caution needed in observational analyses

New data from the UK on the efficacy of mpox MVA-BN vaccine have been published in Lancet Infectious Diseases, together with an editorial comment that highlights major limitations in this and similar studies. [1, 2]

Estimating efficacy of this vaccine is complicated by a lack of prospective data, that the decline in mpox cases predated widespread access to the vaccine, and the significant differences in mpox risk factors between vaccinated and unvaccinated groups.

The new dataset is based on self-completed questionnaires from roughly one-third of the cases reported in the UK from July to October 2022. Overall, only 508/1545 people with confirmed cases returned the questionnaire and the final analysis only included 363/508 cases in gay and bisexual men who provided the required information.

Of these replies, 322/363 (89%) were unvaccinated, 8/363 (2.2%) occurred at least 14 days after vaccination and 32 (8.8%) occurred within 13 days after vaccination. However, by October 2023, actual vaccine coverage was only 47%, so this would have been significantly lower for much of the study period.

Vaccine effectiveness using this case-coverage design was based on coverage at 50% of an estimated 89,000 gay and bisexual men at risk. This compared vaccine coverage among cases with coverage in the eligible population. Rates were also calculated for higher and lower coverage.

Based on these data, three key results were reported.

• The estimated effectiveness at least 14 days after a single dose of MVA-BN was 78% (95% CI: 54 to 89).
• When excluding people older than age 50 (due to likely childhood smallpox vaccination), effectiveness was 74% (95% CI: 43 to 88).
• No early protection was reported within 13 days of the vaccine: –4% (95%CI: –50 to 29).

In sensitivity analyses vaccine effectiveness was 85% (95% CI: 69 to 93) for high-coverage (63% coverage) and 71% (40 to 86) for low-coverage (42% coverage) scenarios.

Breakthrough infections more than 14 days after a vaccine occurred in 8./363 cases, with 4/8 in men living with HIV.

The researchers concluded that a single dose of the MVA-BN vaccine was significantly protective of symptomatic mpox.

The linked editorial notes that major limitations of this study include:

• The low questionnaire return rate.
• The inability to systematically adjust for potential confounders of vaccine effectiveness including age, underlying clinical conditions (such as HIV), previous childhood smallpox vaccination, and behavioural practices related to mpox exposure.
• No data on the likely duration of protection.

Not adjusting for relevant confounders of vaccine effectiveness are significant limitations of two other frequently quoted studies looking at vaccine efficacy. [3, 4]

This is despite numerous studies at CROI 2023 that reported significant differences in both risk and related demographics in people who accessed mpox vaccines. [5, 6, 7, 8, 9, 10]

By Simon Collins, HIV i-Base

References

1. 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).
   https://doi.org/10.1016/S1473-3099(23)00057-9
2. Ogoina D.. Can a single dose of Modified Vaccinia Ankara-Bavarian Nordic vaccine protect against mpox? (13 March 2023).
   https://doi.org/10.1016/ S1473-3099(23)00115-9
3. 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.
4. Sagy YW et al. Real-world effectiveness of a single dose of mpox vaccine in males. Nature Med. DOI: 10.1038/s41591-023-02229-3.9. (31 January 2023).
   https://www.nature.com/articles/s41591-023-02229-3
5. Vaidya A et al. Characteristics and disparities among hospitalized persons with mpox in California. CROI 2023, 19–22 February 2023, Seattle. Poster abstract 902.
   https://www.croiconference.org/abstract/characteristics-and-disparities-among-hospitalized-persons-with-mpox-in-california
   
6. Philpott DCE et al. CD4 count < 350 cells/mm³ increases risk of hospitalization with mpox in PWH. CROI 2023, 19–22 February 2023, Seattle. Poster abstract 903.
   https://www.croiconference.org/abstract/cd4-count-350-cells-mm3-increases-risk-of-hospitalization-with-mpox-in-pwh
7. Corma-Gómez A et al. Mpox virus infection is more severe in patients with uncontrolled HIV infection. CROI 2023, 19–22 February 2023, Seattle. Poster abstract 904.
   https://www.croiconference.org/abstract/mpox-virus-infection-is-more-severe-in-patients-with-uncontrolled-hiv-infection
8. Silva MST et al. Impact of HIV infection on mpox-related hospitalizations in Brazil. CROI 2023, 19–22 February 2023, Seattle. Poster abstract 905.
   https://www.croiconference.org/abstract/impact-of-hiv-infection-on-mpox-related-hospitalizations-in-brazil
9. Garneau WM et al. Clinical outcomes among in- and outpatients with  mpox in an urban health system. CROI 2023, 19–22 February 2023, Seattle. Poster abstract 907.
   https://www.croiconference.org/abstract/clinical-outcomes-among-in-and-outpatients-with-mpox-in-an-urban-health-system
10. Cholli PA et al. Characteristics of patients hospitalized with mpox during the 2022 us outbreak. CROI 2023, 19–22 February 2023, Seattle. Poster abstract 912.
    https://www.croiconference.org/abstract/characteristics-of-patients-hospitalized-with-mpox-during-the-2022-us-outbreak