Infectious Disease · Medical Literature
Examining the immune response of participants receiving Modified Vaccinia Ankara vaccine in Africa (MpoxVax AFRIVAC): a prospective cohort study - protocol
Abstract
Introduction Mpox remains an ongoing global health concern, driven by an ongoing clade I outbreak in Central Africa, which has caused substantial morbidity and mortality. Despite deployment of the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine, data on the durability of vaccine-induced immune responses remain limited, particularly in African populations, women and people with HIV, highlighting the need for context-specific immunogenicity data. Methods and analysis Mpox-Vax AFRIVAC is a prospective, multicentre observational cohort study conducted in Uganda, Tanzania and the Democratic Republic of the Congo (DRC). Adults eligible for MVA-BN vaccination for mpox prevention or who received a first dose within 28 days prior to enrolment are followed for 48 weeks. Serial blood samples are collected to quantify binding antibody responses and assess their durability over time. The primary outcomes are mean geometric MVA-BN-specific antibody titres at week 48 and the rate of antibody decay from week 6 to week 48. Secondary outcomes include antibody kinetics at intermediate time points, factors associated with immune responses, breakthrough infection and vaccine safety. Analyses will use descriptive and longitudinal statistical methods to evaluate immune response trajectories and associated host factors, including HIV status, age and sex. Ethics and dissemination The study is conducted in accordance with the Declaration of Helsinki, registered at the Pan African Clinical Trials Registry (PACTR202601855406764) and publications will be in accordance with the recommendations of the International Committee of Medical Journal Editors. The study has received ethical approvals in Uganda, DRC and Tanzania. Approval for Uganda has been obtained from Uganda Virus Research Institute Research and Ethics Committee (GC/127/1062) and Uganda National Council for Science and Technology (HS5575ES), for DRC from the Institutional Committee of Health ethics (UCB/CIES/PB/001/2025) a
Clinical relevance
The MpoxVax AFRIVAC study addresses a critical evidence gap: despite widespread deployment of the MVA-BN vaccine during an active clade I mpox Public Health Emergency of International Concern, immunogenicity and durability data from African populations—particularly women and people with HIV (PWH)—remain severely limited, with most prior data derived from Caucasian men who have sex with men in high-income settings. Breakthrough infections in vaccinated individuals and rapid antibody waning raise urgent questions about the durability of protection that cannot be answered by existing Western-derived cohort data. Clinicians managing mpox vaccination programmes in endemic and high-burden settings need context-specific evidence to guide decisions on primary schedules, booster timing, and prioritisation of vulnerable subgroups.
Key findings
NOTE: This is a published study protocol, not a completed trial. No efficacy, immunogenicity, or outcome data are yet reported. The following summarises the protocol's pre-specified primary and secondary endpoints as stated in the abstract: 1. Primary endpoint (efficacy metric): Mean geometric MVA-BN-specific binding antibody titres at week 48 post-vaccination, to define the level of humoral immunity sustained at nearly one year. 2. Primary endpoint (kinetic metric): Rate of antibody decay from week 6 to week 48, to characterise the durability curve of vaccine-induced humoral responses in African adults. 3. Secondary endpoints: Antibody kinetics at intermediate time points between week 6 and week 48, providing granular longitudinal trajectories rather than a single end-of-study snapshot. 4. Secondary endpoints: Identification of host-factor determinants of immune response magnitude and durability, specifically HIV serostatus, age, and sex—subgroups historically absent from MVA-BN immunogenicity datasets. 5. Secondary endpoints: Incidence of breakthrough mpox infection in vaccinated participants followed over 48 weeks, enabling real-world assessment of vaccine effectiveness in an endemic clade I setting. 6. Secondary endpoints: Prospective vaccine safety surveillance across all enrolled participants in Uganda, Tanzania, and the DRC. No quantitative effect sizes, confidence intervals, p-values, or NNT/NNH are available, as these are pre-specified outcomes of an ongoing cohort study (approximately 300 participants across three sites, 48-week follow-up).
Practice implications
Until MpoxVax AFRIVAC results are available, clinicians in Central African settings should apply MVA-BN according to current WHO guidance while recognising that approved schedules and booster intervals were validated predominantly in VACV-naïve European men, and may not reflect immunological performance in African women, PWH with CD4 suppression, or clade I–exposed individuals. Particular vigilance is warranted for PWH, in whom existing data suggest attenuated T-cell responses at CD4 counts ≤500/mm³ and potentially reduced antibody durability, supporting a lower threshold for considering a two-dose primary series and monitoring for breakthrough infection. Clinicians and public health programmes should actively support enrolment into and data-sharing from this study, as its findings on antibody decay kinetics and host-factor modifiers will directly inform evidence-based decisions on re-vaccination timing and population-specific dosing strategies in future mpox outbreak responses.