Evaluating the use of dose-sparing vaccination strategies for Monkeypox

The spring-summer 2022 monkeypox outbreak had over 50,000 cases globally, most of them in gay, bisexual, and other men who have sex with men (MSM). In response to vaccine shortages, several countries implemented dose-sparing vaccination strategies, stretching a full-dose vaccine vial in up to 5 fractional-dose vaccines. Recent studies have found mixed results regarding the effectiveness of the monkeypox vaccine, raising the question of the utility of dose-sparing strategies. We used an age- and risk-stratified mathematical model of an urban MSM population in the United States with approximately 12% high-risk MSM to evaluate potential benefits from implementing dose-sparing vaccination strategies in which a full dose is divided in 3.5 fractional-doses. We found that results strongly depend on the fractional-dose vaccine effectiveness (VE) and vaccine supply. With very limited vaccine available, enough to protect with a full-dose approximately one-third of the high-risk population, dose-sparing strategies are more beneficial provided that fractional-dose preserved at least 40% of full dose effectiveness (34% absolute VE), projecting 13% (34% VE) to 70% (68% absolute VE) fewer infections than full-dose strategies. In contrast, if vaccine supply is enough to cover the majority of the high-risk population, dose-sparing strategies can be outperformed by full-dose strategies. Scenarios in which fractional-dosing was 34% efficacious result in almost three times more infections than full-dosing. Our analysis suggests that when monkeypox vaccine supply is limited and fractional-dose vaccination retains moderate effectiveness, there are meaningful health benefits from providing a smaller dose to a larger number of people in the high-risk population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was partially supported by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (UM1AI068635 and UM1AI068617). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Code for this manuscript will be available at repository