Advances and challenges in malaria vaccine development

Abstract

Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa. An effective malaria vaccine would be a valuable tool to reduce the disease burden and could contribute to elimination of malaria in some regions of the world. Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development. The most advanced vaccine candidate, RTS,S, conferred partial protection against malaria in phase II clinical trials and is currently being evaluated in a phase III trial in Africa. New vaccine targets need to be identified to improve the chances of developing a highly effective malaria vaccine. A better understanding of the mechanisms of naturally acquired immunity to malaria may lead to insights for vaccine development.

Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion

“…The quest to develop successful blood-stage malaria vaccines that efficiently block this process have focused on essential parasite proteins like merozoite surface protein 1 (MSP-1) and apical membrane antigen 1 (AMA-1); however, these are highly polymorphic, unable to elicit strain-transcending neutralizing antibodies, and have thus failed in field trials (4). Among the large repertoire of invasionrelated proteins, the family of P. falciparum reticulocyte bindinglike homologous (PfRH) proteins have emerged as key determinants of different invasion pathways (2,3), of which PfRH5 is the only essential conserved parasite ligand (5)(6)(7)(8) that elicits potent strain-transcending neutralizing antibodies (9)(10)(11)(12).…”

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production

“…7 The region of the CSP included in the RTS,S vaccine comprises a number contiguous immunogenic epitopes: (i) a 4-amino-acid (NANP) amino acid repeat sequence that defines an immunodominant B-cell epitope; (ii) a highly variable CD4+ T-cell epitope; (iii) a highly variable CD8+ T-cell epitope and (iv) a conserved "universal" CD4+ T-cell epitope at the C-terminus. 8 Its success is a significant achievement and demonstrates that a recombinant protein vaccine containing only "isolated" B-and T-cell epitopes from a single protein (CSP) delivered on a heterologous carrier can elicit significant protection in humans. Anti-NANP antibodies play a central role in inducing protection by preventing the parasite from infecting the liver and thus blocking progression to red blood cells and clinical malaria.…”

Characterization ofPlasmodium falciparumProteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

“…Because of the complex life-cycle of the parasite and its antigenic make-up, a vaccine design strategy that also incorporates T-cell-mediated immunity has its own benefits. 10 Thus, the T-cell epitopes that promiscuously bind multiple alleles of a human leukocyte antigen (HLA) may be prime targets for future vaccine and immunotherapy development because they seem relevant to a large proportion of the human population. 11 However, the experimental determination of binding specificities for even a single antigen and a single MHC allele is an expensive, laborious, and time-consuming process; at the same time, it is not practical to undertake a binding study of the MHC supertypes, which will involve large numbers of alleles.…”