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Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection.

ABSTRACT: The development of an effective malaria vaccine has remained elusive even until today. This is because of our incomplete understanding of the immune mechanisms that confer and/or correlate with protection. Human volunteers have been protected experimentally from a subsequent challenge by immunization with Plasmodium falciparum sporozoites under drug cover. Here, we demonstrate that sera from the protected individuals contain neutralizing antibodies against the pre-erythrocytic stage. To identify the antigen(s) recognized by these antibodies, a newly developed library of P. falciparum antigens was screened with the neutralizing sera. Antibodies from protected individuals recognized a broad antigenic repertoire of which three antigens, PfMAEBL, PfTRAP and PfSEA1 were recognized by most protected individuals. As a proof of principle, we demonstrated that anti-PfMAEBL antibodies block liver stage development in human hepatocytes. Thus, these antigens identified are promising targets for vaccine development against malaria.

SUBMITTER: Peng K

PROVIDER: S-EPMC5321637 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection.

Peng Kaitian K Goh Yun Shan YS Siau Anthony A Franetich Jean-François JF Chia Wan Ni WN Ong Alice Soh Meoy AS Malleret Benoit B Wu Ying Ying YY Snounou Georges G Hermsen Cornelus C CC Adams John H JH Mazier Dominique D Preiser Peter R PR Sauerwein Robert W RW Grüner Anne-Charlotte AC Rénia Laurent L

Cellular microbiology 20160527 12

The development of an effective malaria vaccine has remained elusive even until today. This is because of our incomplete understanding of the immune mechanisms that confer and/or correlate with protection. Human volunteers have been protected experimentally from a subsequent challenge by immunization with Plasmodium falciparum sporozoites under drug cover. Here, we demonstrate that sera from the protected individuals contain neutralizing antibodies against the pre-erythrocytic stage. To identify ...[more]

PMID: 27130708

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Project description:Malaria-causing Plasmodium parasites have a complex life cycle and present numerous antigen targets that may contribute to protective immune responses. The currently recommended vaccine-RTS,S-functions by targeting the Plasmodium falciparum circumsporozoite protein (CSP), which is the most abundant surface protein of the sporozoite form responsible for initiating infection of the human host. Despite showing only moderate efficacy, RTS,S has established a strong foundation for the development of next-generation subunit vaccines. Our previous work characterizing the sporozoite surface proteome identified additional non-CSP antigens that may be useful as immunogens individually or in combination with CSP. In this study, we examined eight such antigens using the rodent malaria parasite Plasmodium yoelii as a model system. We demonstrate that despite conferring weak protection individually, coimmunizing each of several of these antigens alongside CSP could significantly enhance the sterile protection achieved by CSP immunization alone. Thus, our work provides compelling evidence that a multiantigen preerythrocytic vaccine approach may enhance protection compared to CSP-only vaccines. This lays the groundwork for further studies aimed at testing the identified antigen combinations in human vaccination trials that assess efficacy with controlled human malaria infection. IMPORTANCE The currently approved malaria vaccine targets a single parasite protein (CSP) and results in only partial protection. We tested several additional vaccine targets in combination with CSP to identify those that could enhance protection from infection upon challenge in the mouse malaria model. In identifying several such enhancing vaccine targets, our work indicates that a multiprotein immunization approach may be a promising avenue to achieving higher levels of protection from infection. Our work identified several candidate leads for follow-up in the models relevant for human malaria and provides an experimental framework for efficiently carrying out such screens for other combinations of vaccine targets.

Dataset Information

Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection.

Publications

Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection.

Similar Datasets

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