As monkeypox cases across the world continue to increase, rollouts of the one licensed vaccine are under pressure. In the UK, questions about the number of doses were posed in a letter written by LGBTQ+ groups. In the US, NIH scientists have started to explore “fractional dosing”. The Modified vaccinia Ankara (MVA) that was previously licensed for monkeypox in Canada and the US has been approved by EU counterparts. However, in August 2022, an article in Science called into question the longevity and efficacy of the vaccine. The author, Kai Kupfershmidt, explored the options going forward.  

Originally developed by Bavarian Nordic as a smallpox vaccine, MVA is known to help against monkeypox. Yet “ethical and logistical complexities” of the current crisis are making it hard to establish how much protection it provides. It is difficult to execute “placebo-controlled clinical trials” as the vaccine is already licensed and demand is high.  

Initial evidence that smallpox vaccines might protect against monkeypox emerged in a study in the 1980s. It appeared that smallpox vaccination was “86% effective at preventing monkeypox” among contacts of patients with monkeypox in the Democratic Republic of Congo. As the study was limited, MVA was developed as a “safer alternative” to the older vaccine. Although it was licensed, “its efficacy has barely been tested in people”. Furthermore, its role in “preventing sexual transmission” has not been explored.  

The recommendation of a randomised trial is “ethically dicey”. Therefore, other options must be explored. One cohort in France is using MSM “already enrolled in a study of sexually transmitted diseases – and deemed at high risk of monkeypox”. They will get MVA in the next 2 months, and the researchers will compare infection rates either side of vaccination. A “test-negative” study is also under consideration. This involves investigation of people getting tested for monkeypox, comparing the numbers of vaccinated patients among the positive and negative groups. Dr Michael Marks, of the London School of Hygiene and Tropical Medicine, suggests that this is “probably the strongest nonrandomised approach”.  

Unfortunately, this approach requires “good linkage between testing and vaccination data”. Furthermore, these data can’t demonstrate immunity over time, or “whether disease severity is different among the vaccinated and unvaccinated”.  

Dr Will Nutland, co-founder of Prepster, suggests that these unanswered questions will continue to complicate messaging to high-risk groups. However, he wants to impress upon everyone the importance of getting vaccinated.  

“It is better to receive some level of protection than no protection at all.”  

To participate in a day of monkeypox discussion at the World Vaccine Congress in Europe 2022 head here to get your tickets!