Optivants – Optimising vaccination for iNTS disease in Africa
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Date
2021-07-26
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Kamuzu University of Health Sciences
Abstract
Study 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.