Abstract
Induction of humoural immunity is critical for clinical protection against malaria. More than 100 malaria vaccine candidates have been investigated at different developmental stages, but with limited protection. One of the roadblocks constrains the development of malaria vaccines is the poor immunogenicity of the antigens. The objective of this study was to map the linear B-cell epitopes of the Plasmodium falciparum erythrocyte invasion-associated antigens with a purpose of understanding humoural responses and protection. We conducted a large-scale screen using overlapping peptide microarrays of 37 proteins from the P. falciparum parasite, most of which are invasion-associated antigens which have been tested in clinical settings as vaccine candidates, with sera from individuals with various infection episodes. Analysis of the epitome of the antigens revealed that the most immunogenic epitopes were predominantly located in the low-complexity regions of the proteins containing repetitive and/or glutamate-rich motifs in different sequence contexts. However, in vitro assay showed the antibodies specific for these epitopes did not show invasion inhibitory effect. These discoveries indicated that the low-complexity regions of the parasite proteins might drive immune responses away from functional domains, which may be an instructive finding for the rational design of vaccine candidates.
Highlights
Malaria elimination efforts have yielded outstanding achievements in the past 20 years, and malaria eradication by 2050 was proposed by the Lancet Commission [1]
The Antigenic Epitopes of Critical P. falciparum Antigens Depicted by Peptide Microarray Screening
Microarray screening of the peptide profile was carried out with 289 sera samples from patients suffering from falciparum malaria (FM) and 144 healthy individuals as controls
Summary
Malaria elimination efforts have yielded outstanding achievements in the past 20 years, and malaria eradication by 2050 was proposed by the Lancet Commission [1]. More than half of the world’s countries are malaria free [2], the currently available tools and approaches will not be sufficient to achieve the optimal goal of malaria eradication. A potent vaccine has been believed to be the most cost-effective tool for reducing the negative impact of the disease on human health and is essential for complete malaria eradication. The world’s first malaria vaccine, RTS,S/AS01, is being deployed in a pilot roll-out in three African countries [3]. The clinical protection obtained after immunization has not been as satisfactory as expected, antigen-specific responses were sufficiently elicited [4, 5]. The immunogenic determinants of malarial antigens in connection with clinical protection are two critical aspects that have not been fully understood
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