Sequence analysis of the merozoite surface protein 7 (PvMSP-7) multigene family: vaccine candidates for Plasmodium vivax



Cheng, C
(2018) Sequence analysis of the merozoite surface protein 7 (PvMSP-7) multigene family: vaccine candidates for Plasmodium vivax. PhD thesis, University of Liverpool.

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Abstract

P. vivax is found predominantly in Asia and the emergence of resistance to antimalarial drug and insecticides are major challenges to control of vivax malaria. Control is further complicated by the dormant liver stage of P. vivax, which produces an asymptomatic parasite reservoir. Malaria vaccine development is recognised as the most efficient control intervention globally. Currently, malaria vaccine development is concentrated in P. falciparum and RTS,S has been the most promising vaccine. This has encouraged similar initiatives to develop a P. vivax vaccine. The subject of this thesis is the Plasmodium vivax merozoite surface protein 7 (PvMSP-7), which forms a multi-protein complex with other merozoite surface proteins and plays a principal role in erythrocyte invasion. Studies in P. falciparum have shown that targeting MSP-7 can impair erythrocyte invasion and regulate disease severity. For this reason, PvMSP-7 is a plausible vaccine candidate. However, several questions remain to be addressed before a vaccine can be developed; (i) the antigenic variation and expression pattern of the PvMSP-7 multigene family, (ii) which PvMSP-7 paralog is the most promising target, and (iii) which domain of the protein is most antigenically relevant. The main aim of this thesis is to characterise the structural and expression variation in PvMSP-7 paralogs in the Thai clinical setting, to pinpoint the optimal PvMSP-7 antigen for malaria vaccine development. The conclusion of the thesis is that, of the 13 PvMSP-7 paralogs, PvMSP-7A is the most promising malaria vaccine candidate, being least polymorphic across parasite populations, expressed throughout the bloodstream infection cycle, and containing the greatest number of immunogenic B-cell epitopes. These immunogenic epitopes may confer a two-fold advantage in eliciting immunity and by impairing host cell invasion. This thesis provides a basis for the development of PvMSP-7A as an experimental vaccine, leading to the sustainable prevention of vivax malaria across the world.

Item Type: Thesis (PhD)
Divisions: Fac of Health & Life Sciences > Institute of Infection and Global Health
Depositing User: Symplectic Admin
Date Deposited: 01 Feb 2019 13:08
Last Modified: 08 May 2020 20:22
DOI: 10.17638/03028940
Supervisors:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3028940