IP24-017 - Collaborative research on influenza and other respiratory pathogens in South Africa

PROJECT SUMMARY This project aims to generate a body of data that will result in improved approaches for disease surveillance and prevention and expanded access to interventions for the reduction of morbidity and mortality associated with influenza and other respiratory pathogens in South Africa and the African

region. Specifically (Objective 1, Project 1), we aim to expand and evaluate digital participatory surveillance (DPS) in South Africa. If found to provide valid and useful data on trends in respiratory illness and health-seeking behavior, we will expand this platform in collaboration with neighbouring

countries with limited laboratory infrastructure and evaluate it as a system for monitoring seasonal respiratory illness and identifying outbreaks in the African region. We will also (Objective 1, Project 2) evaluate right-sizing for influenza genomic surveillance through an evaluation of whether the timing,

geographic and demographic distribution of influenza genomic sequence data affects the reported dominance and diversity of circulating viruses to guide annual influenza vaccine composition. This will have a training component to increase regional capacity for next generation sequencing and will provide data to guide WHO and CDC on the optimum number and geographic distribution of sentinel

sites needed to facilitate public health decisions. As part of our strategy to strengthen the NICD’s role as a national and regional influenza reference laboratory we will develop and implement influenza microneutralization (MN) assays (Objective 1, Project 3). These assays will be used to better characterize immune responses to influenza infection or vaccination, demonstrate the role of sero-

epidemiology for public health surveillance and enable testing of sera collected in vaccine trials. We will also develop a high throughput influenza multiplex immunoassays (MIA) to characterize the immune response to influenza infection and vaccination (Objective 1, Project 4). Once successfully optimized this assay will be used to conduct antibody landscape studies from cohort participants in

the CDC-funded HUTS and PHIRST studies and evaluate vaccine trial participant responses. In future years, these antibody landscape analyses, combined with high-resolution cohort data (including infection and vaccination histories) and whole genome sequencing data from participants, will generate foundational knowledge on population-level immune response and how this drives viral

evolution. The ultimate goal of this work would be to develop a framework in which population serology data is incorporated into the WHO vaccine strain update process. We will conduct a phase 2 double-blinded, randomized, controlled trial to evaluate the vaccine efficacy, safety, and immunogenicity of a seasonal inactivated influenza vaccine and a comparator vaccine, in healthy

South Africans (Objective 2, Project 5). This study will aim to understand the mechanism by which different influenza vaccines prevent illness and the potential impact of different vaccines on onward transmission. Ultimately this would be part of a roadmap to ensure increased access to influenza vaccines in Africa. Lastly (Objective 3, Project 6), we aim to scale up and maintain increased influenza

uptake among groups at increased risk of severe influenza illness by understanding the drivers of low influenza vaccination uptake and challenges in current influenza vaccination campaigns, and implementing strategies targeted at these drivers.