A recent study conducted by the European Centre for Disease Prevention and Control (ECDC), the World Health Organization (WHO), and national public health institutes across four European countries has suggested that childhood smallpox vaccination might offer protection against monkeypox virus (MPXV) clade II infections in men. However, the degree of protection appears to vary significantly among the countries studied, underscoring the need for further research to validate these findings. The study, published in Eurosurveillance, analyzed data from Denmark, France (mainland), the Netherlands (mainland), and Spain, focusing on the potential protective effects of historical smallpox vaccination during childhood against laboratory-confirmed monkeypox (mpox) cases.
The 2022–2023 mpox outbreak in Europe predominantly affected men in specific high-risk groups, particularly those engaged in certain behaviors that increased their risk of exposure. This prompted researchers to explore the effectiveness of smallpox vaccines administered during childhood in preventing mpox, aiming to provide insights into current vaccination strategies.
In June 2022, the European Medicines Agency (EMA) approved the use of Imvanex, a vaccine known as Modified Vaccinia Ankara – Bavarian Nordic (MVA-BN), for the prevention of mpox under special conditions. This vaccine is also authorized in the U.S. as JynneosTM and in Canada as ImvamuneTM, where it is used to protect against smallpox, mpox, and other related viruses. These vaccines are the third generation of smallpox vaccines and do not replicate in the body.
The study utilized case-based surveillance data from the aforementioned countries, all of which had recorded information on prior smallpox vaccination status of mpox cases. These countries also provided data on historical smallpox vaccination coverage, which was crucial for the analysis. Researchers focused on individuals born during the peak years of national smallpox vaccination campaigns, which in these countries extended until 1971. Due to the low number of mpox cases reported in females, the study was limited to male cases only.
To estimate vaccine effectiveness, the study employed logistic regression according to the Farrington screening method. Vaccine effectiveness and corresponding 95% confidence intervals (CI) were calculated for each country, followed by a pooled estimate using a random effects model.
Historical data indicated that smallpox vaccination coverage was high (80–90%) across all four countries until the late 1960s, with a notable decline in the final decade of the vaccination programs. However, the estimated effectiveness of prior smallpox vaccination against mpox caused by MPXV clade II varied considerably between the countries. For instance, the Netherlands reported a vaccine effectiveness of 42%, while Spain’s estimate was much higher at 84%. This wide range in effectiveness might be attributed to differences in national booster strategies during the smallpox vaccination campaigns.
The pooled vaccine effectiveness estimate across all four countries was 70%, but with a wide 95% confidence interval ranging from 23% to 89%, indicating a significant degree of uncertainty. Despite these findings suggesting that historical childhood smallpox vaccination could protect approximately two-thirds of men against mpox caused by MPXV clade II, the variability in protection between countries and the broad confidence intervals highlight the need for caution in interpreting the results.
The study’s authors emphasize that these findings are not robust enough to justify differential vaccination strategies against mpox based solely on historical smallpox vaccination status or age. Given the recent increase in mpox cases caused by clade Ib in Central and East Africa, the authors call for urgent studies to assess the effectiveness of the smallpox vaccine against newer circulating strains of the virus.
In conclusion, while the study provides valuable insights into the potential protective effects of smallpox vaccination against mpox, it also raises important questions about the reliability of these findings across different populations. The researchers recommend that individuals at high risk of mpox exposure should be offered vaccination, regardless of their smallpox vaccination history, to ensure broader protection against the virus. Further research is crucial to confirm these findings and to guide effective vaccination strategies in the future.
References
- Colombe S, Funke S, Koch A, Haverkate M, Monge S, Barret AS, et al. Effectiveness of historical smallpox vaccination against mpox clade II in men in Denmark, France, the Netherlands and Spain, 2022. Eurosurveillance. 2024 Aug 22;29(34):2400139.
- Gessain A, Nakoune E, Yazdanpanah Y. Monkeypox. New England Journal of Medicine. 2022 Nov 9;387(19):1783–93.