@article{08698e1f6cb34624a8ecd6e538de8948,
title = "A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection",
abstract = "The Plasmodium falciparum protein, apical membrane antigen 1 forms a complex with another parasite protein, rhoptry neck protein 2, to initiate junction formation with the erythrocyte and is essential for merozoite invasion during the blood stage of infection. Consequently, apical membrane antigen 1 has been a target of vaccine development but vaccination with apical membrane antigen 1 alone in controlled human malaria infections failed to protect and showed limited efficacy in field trials. Here we show that vaccination with AMA1-RON2L complex in Freund's adjuvant protects Aotus monkeys against a virulent Plasmodium falciparum infection. Vaccination with AMA1 alone gave only partial protection, delaying infection in one of eight animals. However, the AMA1-RON2L complex vaccine completely protected four of eight monkeys and substantially delayed infection (>25 days) in three of the other four animals. Interestingly, antibodies from monkeys vaccinated with the AMA1-RON2L complex had significantly higher neutralizing activity than antibodies from monkeys vaccinated with AMA1 alone. Importantly, we show that antibodies from animals vaccinated with the complex have significantly higher neutralization activity against non-vaccine type parasites. We suggest that vaccination with the AMA1-RON2L complex induces functional antibodies that better recognize AMA1 as it appears complexed with RON2 during merozoite invasion. These data justify progression of this next generation AMA1 vaccine towards human trials.",
author = "Prakash Srinivasan and Baldeviano, {G. Christian} and Kazutoyo Miura and Ababacar Diouf and Ventocilla, {Julio A.} and Leiva, {Karina P.} and Luis Lugo-Roman and Carmen Lucas and Sachy Orr-Gonzalez and Daming Zhu and Eileen Villasante and Lorraine Soisson and Narum, {David L.} and Pierce, {Susan K.} and Long, {Carole A.} and Carter Diggs and Duffy, {Patrick E.} and Lescano, {Andres G.} and Miller, {Louis H.}",
note = "Funding Information: 1Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA; 2US Naval Medical Research Unit No. 6 (NAMRU-6), Callao, Peru; 3Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA; 4US Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, MD, USA; 5Malaria Vaccine Development Program, U.S. Agency for International Development, Washington, DC, USA and 6Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA Correspondence: Prakash Srinivasan (psriniv3@jhu.edu) or Louis H. Miller (lmiller@niaid.nih.gov) 7Present address: Johns Hopkins Malaria Research Institute, Dept. Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Funding Information: P.S., G.C.B., E.V., L.S., C.D., P.E.D., A.G.L., and L.H.M. designed and reviewed the animal study protocol; P.S., K.M., and A.D. designed and performed the immunogenicity and GIA assays; P.S. designed and performed the competition assay for blocking antibodies and biacore; D.Z., D.L.N. produced and verified the recombinant AMA1 proteins; P.S., G.C.B., J.A.V., S.O.-G. and L.L.-R. assisted with the malaria challenge; J.A. V., K.P.L., C.L. and S. O.-G. assisted with parasitological monitoring; L.L.-R. supervised the clinical care of the Aotus monkeys; P.S., and K.M. evaluated all the data and performed statistical analyses; S.K.P. contributed to the design of experiments and analysis of data; P.S. and L.H.M. led the study and wrote the paper. All the co-authors contributed to writing the manuscript. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases and by the U.S. Agency for International Development (USAID). Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41541-017-0015-7",
language = "English (US)",
volume = "2",
journal = "npj Vaccines",
issn = "2059-0105",
publisher = "Nature Publishing Group",
number = "1",
}