Project: Determining Correlates of Naturally Acquired Pre-Erythrocytic Immunity to Plasmodium falciparum Malaria in an Experimental Human Challenge Model

Acronym	CoNAIPS (Reference Number: TMA2016SF-1513)
Duration	01/04/2019 - 31/03/2024
Project Topic	Plasmodium falciparum (Pf) malaria remains a major public health problem affecting the health and economic wellbeing of over 50% of sub-Saharan Africa’s population. In the absence of preventative vaccination, the situation is unlikely to be transformed in the foreseeable future. The development of an effective malaria vaccine has been difficult, and would greatly benefit from a better understanding of the mechanisms that mediate naturally acquired immunity (NAI) in individuals with life-long exposure. A vaccine with protective efficacy against malaria is feasible, as several current approaches have achieved some success. Vaccinations with RTS,S/AS01, based on the abundant sporozoite-surface circumsporozoite protein, and vaccination with viral vectors encoding the pre-erythrocytic antigen ME-TRAP, both confer immunity to malaria in human trials. However, neither vaccination approach is sufficiently protective in their current forms, and additional approaches are required. It is generally thought that NAI does not confer sterile protection. Furthermore, most naturally acquired responses (studied so far) are directed to the erythrocytic stages rather than pre-erythrocytic stages of the parasite’s life cycle. It is therefore unknown whether NAI is a useful model to guide the design of improved preerythrocytic vaccines. However, we have recently observed that a proportion of exposed adults (about 10% (4 out of 37)), do not develop blood stage parasitaemia following experimental controlled human malaria infections (CHMI) delivered by an intravenous dose of live sporozoites. This dose of live sporozoites has been shown to result in 100% infection in individuals with no prior exposure to malaria, suggesting that exposed adults may have functional pre-erythrocytic immunity. This proposal seeks to utilize the recently established experimental CHMI approach in exposed individuals, to determine mechanisms and antigen-specific correlates of pre-erythrocytic immunity, from adults that remain blood-stage parasite negative after infection. This approach will allow for a more detailed characterization of defined immune responses prior to controlled infection with parasites in a way that is not possible in observational field studies. Data on the association between immune responses and outcomes of infection will lead to the advancement and prioritisation of the most promising antigen-specific targets for further development as vaccine candidates.
Network	EDCTP2
Call	Senior Fellowships 2016

Project partner

Number	Name	Role	Country
1	African Research Collaboration for Health Ltd.	Coordinator	Kenya