Determinants of Vaccine Responses in Low-Income Countries (LICs)

PROJECT SUMMARY By mentoring junior investigators from the United States and low-come countries (LICs) in patient- oriented research (POR) in global health, particularly in vaccine-preventable diseases, I hope to build local capacity, improve outcomes and reduce health disparities. Working within the resource-limited health systems in LICs is challenging, and the influences of co-infections (particularly parasitic infections), anemia, undernutrition, and various microorganisms on vaccine efficacy may be underappreciated. For these reasons, vaccines and vaccine campaigns developed for and assessed in high-income countries (HICs) cannot be assumed to be feasibly implemented or to perform similarly in LICs. For instance, SARS-CoV-2 vaccination with mRNA-based vaccines in sub-Saharan Africa has been limited by the cold-chain requirement of these vaccines. Cultural and socio-economic factors have led Malawians to generally choose receiving the single dose Ad26.COV2-S rather than the ChAdOx1 vaccine. Growing evidence suggests that performance of vaccines in LICs is lower than HICs and the protective immunity elicited by some vaccines is shorter than originally anticipated. In an interconnected world where diseases do not have borders, optimizing interventions to control transmittable diseases in LICs impacts the health of populations worldwide. The overall goal is to train junior investigators across disciplines to optimize vaccinations in Malawi, a sub-Saharan African country in which I have established a thriving research infrastructure. The first two aims of this application, supported by my R01AI164686-funded project, will assess i) the longevity of antibodies (magnitude and function) and memory cells induced by the Ad26.COV2-S SARS-CoV-2 vaccine; ii) the contribution of pre-existing changes in innate immunity to these responses; iii) the association of malaria, micronutrient deficiency, and microorganisms colonizing the nasopharynx with these responses. In the third aim, funded through this proposal, we will address the longevity of five childhood vaccines, focusing particularly on optimizing the timing of re-vaccination. The importance of this question became obvious in 2023 when three poliovirus cases were identified in Malawi. The Ministry of Health, with no relevant data available, decided to revaccinate all children with an arbitrary cutoff of 15 years of age. I have mentored several investigators in POR, particularly from Malawi, and have been conducting research in the immunoepidemiology of vaccines in LICs (including Malawi) since 2015. With this award, I would be able to expand my panel of trainees, devote more time to each of them, acquire training to further my mentorship skills as well as my own professional skillset, and expand the focus of the research to include other childhood vaccines. With the research infrastructure built in Malawi, I am now well-equipped to successfully train clinician scientists and other junior investigators in POR in infectious diseases, particularly in vaccines in LICS.