RR\ID Evidence Scale rating by reviewer:
Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.
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Review: The manuscript "Optimal deployment of limited vaccine supplies to combat mpox" investigates a very timely question: given that countries most affected by mpox outbreaks do not have sufficient vaccines, should standard two-dose vaccination schedules be followed, or are cases reduced if more people receive a first dose? Using a simple model, the authors conclude that the latter is the case, unless a subset of the population is at substantially higher risk of infection. The manuscript is well-written and limitations of the study are clearly described.
Strengths of the study:
The authors acknowledge that detailed data on a number of key parameters (e.g., vaccine effectiveness and waning) to properly answer the public health-relevant question is still missing. This lack of data limits the type of modeling that is possible and I agree with the choice of a very simple model. More complex models, e.g., commonly used compartmental disease models, that predict the spread of the virus could not be reliably parametrized and predictions could thus not be trusted. Given the high uncertainty associated with key parameters, the findings should not be interpreted quantitatively. The authors carefully describe this as well as further limitations of their study. The study highlights the need to accurately estimate mpox-related parameters for better public-health decision-making. Assuming limited available data on mpox vaccine effectiveness is correct and the protection induced by one versus two doses does not differ much, this model-based study indicates strong evidence that vaccination of more people with a single dose (rather than fewer people with two doses) can reduce disease incidence, as well as the incidence of severe disease and hospitalization.
Implications for public health decision-making:
Policy makers should be encouraged by the study results to diverge from common practice and provide as many people as possible with a single dose of mpox vaccine. However, it is important to be aware of the explicitly stated and implicit limitations of the study and its findings. Specifically, policy makers must consider the spatial heterogeneity in infection rates that exists in affected countries, which could understandably not be considered in this study. Moreover, public health agencies dedicate resources to derive better estimates for some of the key parameters that underlie the important investigated research question.
Specific comments:
The sentence "In our own meta-analysis we estimated very similar vaccine effectiveness of 74% after one dose and 82% after two doses." requires a reference to this meta-analysis, or, if this analysis was conducted as part of this study, much more details need to be shown.
The sentence "a one-dose vaccination schedule is predicted to avert 1.80-fold (CI: 1.50-1.92)" requires more information. At a minimum, the word "symptomatic infections" or "cases" needs to be added. Otherwise, it is unclear whether infections, severe infections or deaths are reduced by 1.8-fold by a one-dose vaccination schedule.
The word "more" needs to be added here: "or of MORE severe outcomes than others"