Every year, more than 2 million people die globally from infections caused by mucosal pathogens like *Streptococcus pneumoniae*, *Neisseria meningitidis*, and Group B Streptococcus—most of them in low- and middle-income countries (LMICs). Vaccines have cut child deaths, but their long-term effectiveness is undermined by a poor understanding of how these bacteria spread and evolve in populations facing co-infections, malnutrition, and different climates. This research unit will study how these pathogens are carried and transmitted in African communities, develop better ways to measure protective immunity beyond standard antibody tests, and optimise vaccine dosing and scheduling for LMIC settings. If successful, the work could improve how vaccines are deployed to achieve herd protection, slow the emergence of antimicrobial resistance, and reduce the burden of life-threatening endemic and epidemic disease. The findings may also inform global vaccination policy and strengthen research capacity in partner countries through training and infrastructure investment.
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a) UCL STRATEGY: MPRU embodies UCL’s Global Health Grand Challenge, bringing together internationally leading investigators to find solutions to global health problems & policy change. UCL 2034 principal themes include academic leadership & excellence; cross-disciplinarity; impact through innovative international partnerships. Excellence in infection GHR has been targeted through Africa Health Research Institute (AHRI) & partnership with leading LMIC centres. b) UCL GHR INFRASTRUCTURE: Infection & Immunity Division houses world-class investigators with complementary expertise in pathogen biology (closely AHRI affiliated). Faculty of Population Health Sciences includes Institutes of Child Health (Vaccinology Research Group) & Global Health. Farr Health Informatics Research Institute uses big data to address population-sized questions (UCL, LSHTM, PHE). MRC Clinical Trials Unit is at forefront of innovative clinical trials in LMICs. UCL will provide MPRU with newly refurbished offices & labs; will commit Director/Co-Directors time; & additional administrative support c) EXISTING PARTNERSHIPS: MPRU will add value by bringing together multi-institutional expertise (>25 senior investigators), capitalising on LMIC partnerships with differing epidemiological, climactic & environmental environments (Malawi, Kenya, Mali, Gambia, South Africa); & UK partners from Edinburgh; Southampton, Oxford, Liverpool & UCL. Links with NIHR HPRU in Immunisation will bring strengths in modelling, programmatic evaluation & national policy making. Partnership with UK Public Health Rapid Support Team will bring internationally leading epidemiological, modelling & social science expertise in epidemic responsiveness. MRC, WT, Gates Foundation funded programmes will be leveraged to achieve greatest impact in LMICs, strengthening research capacity by investing in people (PhD studentships & post-doctoral funding). d) RESEARCH PROGRAMME (see figures) BACKGROUND: Mucosal pathogens e.g. S. pneumoniae, N. meningitidis & Group B Streptococcus (GBS) account for >2M deaths globally & substantial disability, predominately in LMICs. Vaccines have reduced under-5 mortality but more effective control of carriage & transmission is crucial to maintaining long-term effectiveness & limiting AMR emergence Knowledge from resource-rich settings often cannot be extrapolated to LMICs where populations are under complex pressures from co-infections (e.g. HIV, helminths & malaria); malnutrition, climate & environment. We have an incomplete understanding of how to measure herd protection & long term vaccine-induced immunity in LMICs, where carriage patterns differ from high-income countries. There is increasing realisation that conventional antibody-based correlates of protection have limited utility. There is uncertainty about how to effectively dose & schedule new/existing vaccines; & how other non-vaccine interventions e.g. commensal colonisation & population-based antimicrobial prophylaxis will impact on disease STRATEGY: Research will be led by UK-LMIC investigator partnerships, primarily in Africa, focusing in this first phase, on high disease burden URT pathogens & the neonatal pathogen GBS. MPRU team brings together the disciplines required for high quality, innovative, relevant research using cutting-edge laboratory facilities in UK & LMIC centres OVERALL AIM: To address the limitations in long-term effectiveness of current vaccines in LMICs, MPRU aims to reduce mucosal pathogen carriage & transmission to achieve herd protection against life-threatening endemic/ epidemic disease OBJECTIVES: 1) Define mucosal pathogen carriage & transmission biology in LMICs; evaluate impact of bacterial/viral co-infections; derive mathematical models predictive of protection (short-medium term) 2) Generate novel approaches to protective immunity assessment that overcome limitations of antibody correlates (short-medium term) 3) Optimise existing vaccine dosin
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