Date of Award

January 2026

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Luke Davis

Second Advisor

Lauren Pischel

Abstract

Background: In 2022, the global mpox outbreak was declared a Public Health Emergency of International Concern (PHEIC). Although cases declined thereafter, the emergence of the more virulent and transmissible clade Ib led to the reinstatement of mpox as a PHEIC. Despite these evolving threats, real-world evidence on the effectiveness of orthopoxvirus vaccines – MVA-BN, LC16m8, and ACAM2000 – remain limited.Methods: This study represents the third iteration of a living systematic review and meta-analysis, with the latest search conducted on January 30, 2026, updating prior searches from January 2, 2025 and November 3, 2023. The risk of publication bias was conducted through funnel plots and Egger’s test. Study quality was examined through the Newcastle-Ottawa scales. Results: A total of 1,771 records were identified, of which 16 new studies were included. There were 84 studies carried over from prior iterations. This analysis comprised 716 VE estimates across 100 studies. For MVA-BN, pooled VE against mpox infection was 75% (95%CI 66-84%) for one dose and 83% (95%CI 78-88%) for two doses. In contrast, VE for post-exposure prophylaxis (PEP) was low and imprecise (VE 20%, 95%CI -16–56%). Among immunocompromised individuals and people living with HIV, pooled VE was 50% (95%CI 36-63%), although subgroup-specific estimates were limited by sparse CD4-stratified data. For severity outcomes, vaccination was associated with reduced risk of hospitalization (VE 70%, 95%CI 63-77%), fewer rash locations (VE 57%, 95%CI 35-71%), and decreased constitutional symptoms and lymphadenopathy (VE 46%, 95% CI 36-56%). No new studies evaluated VE in children or pregnant individuals, nor were there updates on protection against specific rash types or mucosal complications. Conclusion: The MVA-BN vaccine demonstrates high effectiveness against mpox infection after both one and two doses. It also seems to display reduced hospitalization due to mpox, rash distribution, and constitutional symptoms and lymphadenopathy. However, PEP effectiveness remains uncertain, and evidence in immunocompromised populations, children, and pregnant individuals is limited. The absence of robust effectiveness data for LC16m8 and ACAM2000, as well as for emerging subclades such as clade Ib, highlights important gaps in the evidence base and priorities for future research.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 09/16/2027

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