Breadth of humoral response and antigenic targets of sporozoite‐inhibitory antibodies associated with sterile protection induced by controlled human malaria infection |
| |
| Authors: | Kaitian Peng Yun Shan Goh Anthony Siau Jean‐François Franetich Wan Ni Chia Alice Soh Meoy Ong Benoit Malleret Ying Ying Wu Georges Snounou Cornelus C Hermsen John H Adams Dominique Mazier Peter R Preiser Robert W Sauerwein Anne‐Charlotte Grüner Laurent Rénia |
| |
| Institution: | 1. Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore;2. School of Biological Sciences, Nanyang Technological University, Singapore;3. Centre d'Immunologie et de Maladies Infectieuses (CIMI) – Paris, Institut National de la Santé et de la Recherche Médicale (Inserm) U1135 – Centre National de la Recherche Scientifique (CNRS) ERL 8255, Paris, France;4. Sorbonne Universités, UPMC Univ Paris 06, UPMC UMRS CR7, Paris, France;5. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;6. Department of Medical Microbiology, Radboud University, Nijmegen Medical Center, Nijmegen, Netherlands;7. Department of Global Health, College of Public Health, University of South Florida, Tampa, USA;8. AP HP, Centre Hospitalo‐Universitaire Pitié‐Salpêtrière, Paris, France |
| |
| 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. |
| |
| Keywords: | |
|
|
