Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783256310585753600 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5551459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT srinivasanprakash amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT baldevianogchristian amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT miurakazutoyo amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT dioufababacar amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT ventocillajulioa amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT leivakarinap amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT lugoromanluis amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT lucascarmen amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT orrgonzalezsachy amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT zhudaming amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT villasanteeileen amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT soissonlorraine amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT narumdavidl amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT piercesusank amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT longcarolea amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT diggscarter amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT duffypatricke amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT lescanoandresg amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT millerlouish amalariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT srinivasanprakash malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT baldevianogchristian malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT miurakazutoyo malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT dioufababacar malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT ventocillajulioa malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT leivakarinap malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT lugoromanluis malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT lucascarmen malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT orrgonzalezsachy malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT zhudaming malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT villasanteeileen malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT soissonlorraine malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT narumdavidl malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT piercesusank malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT longcarolea malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT diggscarter malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT duffypatricke malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT lescanoandresg malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection AT millerlouish malariavaccineprotectsaotusmonkeysagainstvirulentplasmodiumfalciparuminfection |