Optivants – Optimising vaccination for iNTS disease in Africa

dc.contributor.authorGordon, Melita
dc.date.accessioned2021-12-21T12:01:50Z
dc.date.available2021-12-21T12:01:50Z
dc.date.issued2021-07-26
dc.description.abstractStudy design: Prospective systems serology analysis of serological samples collected in several studies of children 0-5 years across sub-Saharan Africa: 1. STRATAA – 500-1000 paired samples available collected between 2015-2018 in peri-Urban Malawi, 2. SAiNTS 2000 paired samples due to be collected 2021-2022, 3. 1000 single samples VacciNTS sites in Kenya, Burkina Faso, Ghana 2021-2022. Problem statement: Invasive non-Typhoid salmonella (iNTS) is responsible for >500,000 illnesses, 77,500 deaths, and the loss of 4,263,500 DALYs every year. Despite its high burden, iNTS remains a Neglected Infectious Disease. It is pre-dominantly a disease of infants in sub-Saharan Africa (sSA). Although risk is amplified by HIV co-infection, this is a factor in only a minority of paediatric cases. The key feature of severe infection is systemic spread from the gut to systemic sites. The two major strategies to control these invasive infections are antimicrobial treatment and vaccination. However, emerging anti-microbial resistance limits benefit and there is no licensed vaccine currently available against iNTS. Broad Objective: To comprehensively elucidate the effector functional humoral profiles and antigenspecificities of protective antibody against iNTS to define a correlate of humoral protection that can be applied to vaccine design and evaluation. Specific Objectives: 1. Identify key novel antigens (Ags), in addition to those already known, that induce protective antibodies (Abs). 2. Describe the mechanisms of action by which different subclasses of antibodies control NTS. 3. To contextualize the value of single-antigens vs multi-component vaccines against iNTS 4. Understand how different co-morbidities (malaria, malnutrition, and anaemia) modulate these functional immune responses and specific protective functions. 5. Provide robust Correlates of Protection (CoP) to accelerate licensure of both current and new vaccines. Methodology: This will be a lab based cross-sectional study conducting systems serology analysis utilising pre-existing serological samples from approved studies in Malawi and across sub-Saharan Africa. STRATAA samples will be utilized for the antigen discovery phase, SAiNTS samples are set for evaluating the range of antigenic exposure to different NTS strains right across the continent, and detailed characterisation of susceptibilities, allowing further dissection and validation of the systems serology signature, to be layered onto the findings from the initial STRATAA discovery cohort. Expected findings and their dissemination: Firstly, Identification of functional-correlates of protection which may provide critical insights for the selection of promising adjuvants that may directly influence the functional (isotype, subclass, and Fc-glycosylation) quality of the humoral immune response. Secondly, data generated under this consortium is likely to provide key insights into the specific assays that interrogate and capture readouts of protective immunity. Linked to Ag discovery, qualified, and validated assays may be rapidly developed and deployed to support the evaluation of current and future vaccines. Finally, these data may provide critical clues for the generation of functionally optimized monoclonal therapeutics that can act to complement or replace current antibiotic strategies, considering the emergence of multi-drug resistance. The results will be presented locally (MLW, COMREC and Joint COM/MLW Research Dissemination conference), nationally, and internationally including other partner sites in the sero-epidemiology work package of the VacciNTS consortium contributing to key knowledge for vaccine development and deployment. This will have relevance for policy decision regarding iNTS control in Malawi and other sub-Saharan African countries. Results will be submitted for publication in a peer reviewed academic journal.en_US
dc.description.sponsorshipMalawi Liverpool Welcome Trust 90% Kamuzu University of Health Sciences 10%en_US
dc.identifier.urihttp://rscarchive.kuhes.ac.mw/handle/20.500.12988/721
dc.language.isoenen_US
dc.publisherKamuzu University of Health Sciencesen_US
dc.relation.ispartofseriesprotocol;P.04/21/3297
dc.titleOptivants – Optimising vaccination for iNTS disease in Africaen_US
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