The Role of FC Dependent Mechanisms in Vaccine-Induced Protection at KEMRI Wellcome Trust Research Programme (KWTRP)

The Role of fc Dependent Mechanisms in Vaccine-induced Protection among Adults Living in Malaria Endemic Areas

• Malaria continues to be a major public health concern despite considerable investment. In 2022, there were an estimated 249 million cases, with approximately 608,000 malaria deaths
• The approval of RTS, S/AS01B (MosquirixTM, GSK) and, more recently, R21/matrix M as candidate vaccines by the WHO have renewed hope for malaria control. Both vaccines are based on an immunodominant P. falciparum circumsporozoite protein (CSP)(2, 3).
• Despite demonstrable efficacy, both vaccines suffer from waning levels of protection and may require additional booster doses. Further, both fall below the >90% efficacy level required for malaria eradication.
• Therefore, the development of more efficacious next-generation vaccines is important. We used a controlled human challenge model to investigate vaccine-associated correlates of protection in adults living in a malaria-endemic region. Although licenced, a better understanding of R21/MM and/or RTS, S/AS01B antibody response and functions is important to inform future vaccine design. It is known that R21/MM and RTS, S induce a strong and sustained anti-NANP IgG response in both children and adults, which is associated with vaccine efficacy.
• However, the factors affecting variable vaccine efficacy in malaria-exposed adults remain incompletely understood. Antibody Fc-mediated mechanisms correlate strongly with protective immunity for P. falciparum. These include fixing and activating serum complement to enhance neutralisation and killing of malaria parasites and interacting with Fc-receptors (FcRs) expressed on phagocytes to promote cellular killing (opsonic phagocytosis and antibody-dependent cellular (4, 5).
• The goal of this project is to explore the level and durability of anti-NANP specific antibody-dependent functional antibodies using bead-based antigen-specific Fc- mediated functions adopted within our group.