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A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection

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...

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Autores principales: Srinivasan, Prakash, Baldeviano, G. Christian, Miura, Kazutoyo, Diouf, Ababacar, Ventocilla, Julio A., Leiva, Karina P., Lugo-Roman, Luis, Lucas, Carmen, Orr-Gonzalez, Sachy, Zhu, Daming, Villasante, Eileen, Soisson, Lorraine, Narum, David L., Pierce, Susan K., Long, Carole A., Diggs, Carter, Duffy, Patrick E., Lescano, Andres G., Miller, Louis H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551459/
https://www.ncbi.nlm.nih.gov/pubmed/28804644
http://dx.doi.org/10.1038/s41541-017-0015-7
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author Srinivasan, Prakash
Baldeviano, G. Christian
Miura, Kazutoyo
Diouf, Ababacar
Ventocilla, Julio A.
Leiva, Karina P.
Lugo-Roman, Luis
Lucas, Carmen
Orr-Gonzalez, Sachy
Zhu, Daming
Villasante, Eileen
Soisson, Lorraine
Narum, David L.
Pierce, Susan K.
Long, Carole A.
Diggs, Carter
Duffy, Patrick E.
Lescano, Andres G.
Miller, Louis H.
author_facet Srinivasan, Prakash
Baldeviano, G. Christian
Miura, Kazutoyo
Diouf, Ababacar
Ventocilla, Julio A.
Leiva, Karina P.
Lugo-Roman, Luis
Lucas, Carmen
Orr-Gonzalez, Sachy
Zhu, Daming
Villasante, Eileen
Soisson, Lorraine
Narum, David L.
Pierce, Susan K.
Long, Carole A.
Diggs, Carter
Duffy, Patrick E.
Lescano, Andres G.
Miller, Louis H.
author_sort Srinivasan, Prakash
collection PubMed
description 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.
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spelling pubmed-55514592017-08-10 A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection Srinivasan, Prakash Baldeviano, G. Christian Miura, Kazutoyo Diouf, Ababacar Ventocilla, Julio A. Leiva, Karina P. Lugo-Roman, Luis Lucas, Carmen Orr-Gonzalez, Sachy Zhu, Daming Villasante, Eileen Soisson, Lorraine Narum, David L. Pierce, Susan K. Long, Carole A. Diggs, Carter Duffy, Patrick E. Lescano, Andres G. Miller, Louis H. NPJ Vaccines Article 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. Nature Publishing Group UK 2017-05-22 /pmc/articles/PMC5551459/ /pubmed/28804644 http://dx.doi.org/10.1038/s41541-017-0015-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Srinivasan, Prakash
Baldeviano, G. Christian
Miura, Kazutoyo
Diouf, Ababacar
Ventocilla, Julio A.
Leiva, Karina P.
Lugo-Roman, Luis
Lucas, Carmen
Orr-Gonzalez, Sachy
Zhu, Daming
Villasante, Eileen
Soisson, Lorraine
Narum, David L.
Pierce, Susan K.
Long, Carole A.
Diggs, Carter
Duffy, Patrick E.
Lescano, Andres G.
Miller, Louis H.
A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection
title A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection
title_full A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection
title_fullStr A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection
title_full_unstemmed A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection
title_short A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection
title_sort malaria vaccine protects aotus monkeys against virulent plasmodium falciparum infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551459/
https://www.ncbi.nlm.nih.gov/pubmed/28804644
http://dx.doi.org/10.1038/s41541-017-0015-7
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