Title: NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard)
Funder: Department of Health and Social Care

Abstract: Vaccines are extremely effective public health interventions. COVID-19 and recent Ebola outbreaks have brought this to public and political attention. But not everyone benefits equally. Structural factors (social, biological, geographical, political circumstances that determine the benefits of vaccination) render some communities vulnerable, unable to secure optimal health benefits from vaccination programmes. This both drives health inequity and undermines wider vaccine impact by allowing persistence of non-immune communities as foci for recurrent disease outbreaks._x000D_ Our goal is to identify modifiable structural, social and biological determinants of impaired vaccine impact in vulnerable African communities, and hence to develop integrated strategies to address them and to drive health equity._x000D_ VAnguard brings together East African leaders in vaccine research, implementation and community engagement, with UK experts in vaccine biology and the social anthropology of vaccine hesitancy._x000D_ Our specific objectives are, in Uganda and Kenya, to_x000D_ 1. Investigate biological drivers and mechanisms of population differences in vaccine response _x000D_ 2. Understand how structural, social and biological determinants of vaccine response interrelate to determine vaccine impact_x000D_ 3. Identify and model integrated strategies to inform development of future interventions to optimise vaccine impact among vulnerable populations_x000D_ We shall work with national stakeholders to explore vaccine uptake and effects of the COVID-19 pandemic on unrelated vaccine programmes, and identify and engage with communities with (i) poor vaccine uptake and/or (ii) high prevalence of hypothesised biological determinants of poor vaccine impact, such as parasite infection or malnutrition. We shall review literature; we shall use data and samples from our current trials in Uganda (on effects of infection exposure) and Kenya (on nutritional exposure) to identify biomarkers (microbial, nutritional, immunological) indicative of vulnerability to poor vaccine impact. In consultative meetings, initial findings will inform co-design of a community-based VAnguard study. We shall use mixed methods, community engagement and analysis of biological samples to further address objectives 1 & 2. A comprehensive analysis, modelling of possible interventions, and iterative stakeholder & community engagement, will inform co-creation of strategies to optimise vaccine impact for vulnerable communities (objective 3), for testing in future studies._x000D_ Multidisciplinary teams with members from each country, comprising experts and trainees in biological and social science and community engagement, and working with communities and implementation stakeholders, will generate a sustainable, collaborative research culture and facilitate sustainable pathways to research impact. _x000D_ Senior co-applicants will support early (2) & mid-career (2) scientists to lead thematic and study management work packages and co-supervise PhD students (3); cross-cutting leadership, research and research-management training, and vaccinology and modelling training modules, will support personal and institutional capacity strengthening for vaccinology in Africa._x000D_ Outcomes will be (1) new knowledge on interacting structural, social & biological factors that determine vaccine impact, (2) new strategies for optimising vaccine impact for vulnerable communities & (3) strengthened capacity for multidisciplinary, impactful vaccine research in Africa.

Lay abstract: Vaccination is a hugely important public health intervention: key to smallpox eradication, polio elimination, and control of Ebola outbreaks and the COVID-19 pandemic. But not everyone benefits equally. Some vaccines give weaker protection in people from rural, tropical settings than in those from high income settings: for example, BCG for tuberculosis and oral polio vaccine for polio. Some new vaccines, under development, also elicit weaker responses in people living in low-income, rural settings. The biological reasons for this are not fully understood. Also, some people benefit less from vaccines for socioeconomic reasons, such as the social context of the communities they live in, including limited access to accurate information to aid vaccine choices. Social and biological factors can interact to make communities “vulnerable” in terms of vaccine impact. For example, poor people in rural communities with difficulties in vaccine access may also be undernourished or exposed to infections that alter immune responses to vaccination. This needs to be addressed to promote health equity, but also to secure maximum global benefit from vaccines: non-immune communities are foci for recurrent disease outbreaks._x000D_ VAnguard’s goal is to understand how biological and social factors interact to impair vaccine impact in vulnerable African communities, in order to develop integrated strategies to optimise vaccine benefits and drive health equity. _x000D_ VAnguard will bring together African and UK experts in vaccine research, implementation and stakeholder and community engagement, to work in Uganda and Kenya to_x000D_ 1. Investigate how biological factors (such as infections, nutrition) influence vaccine responses_x000D_ 2. Explore how communities perceive and access vaccines, what influences them to take up vaccines for themselves and their families, and how this relates to social vulnerability, biological health status and vaccine information _x000D_ 3. Bring together biological and social data, and engage communities, to work out how vaccination can best be optimised for vulnerable communities, thereby also benefitting entire populations. _x000D_ First, we shall work with national stakeholders (such as Ministries of Health, and vaccine-related non-governmental organisations), review literature, and work on samples from previous studies, to identify Ugandan and Kenyan communities likely to have most difficulty in getting the best out of vaccination programmes (“vulnerable communities”). Then, with stakeholders and communities, we shall co-design the VAnguard Community Study, and implement it to investigate in detail which biological and social factors most influence vaccine impact in vulnerable communities. Data and economic modellers will study the results to identify which factors could usefully be modified, and we shall work with the communities to explore ways in which this could be done. Hence we shall co-develop strategies which national stakeholders may be able to implement straight away, or which can be tested in future studies._x000D_ The work will be led by young African scientists, supported by local and international experts, to build capacity for African vaccine research. Biological, social, and implementation scientists and experts will work closely together to understand each other’s disciplines, establishing a culture of collaboration that will foster sustainable pathways to the desired impact: healthy communities.

Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;3.4 VACCINES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.3 INFLUENCES AND IMPACT
Health categories: GENERIC HEALTH RELEVANCE