Cargando…
Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites
Live attenuated malaria vaccines are more potent than the recombinant protein, bacterial or viral platform vaccines that have been tested, and an attenuated sporozoite vaccine against falciparum malaria is being developed for humans. In mice, attenuated malaria sporozoite vaccines induce CD8(+) T ce...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280278/ https://www.ncbi.nlm.nih.gov/pubmed/22355349 http://dx.doi.org/10.1371/journal.pone.0031247 |
_version_ | 1782223806646976512 |
---|---|
author | Weiss, Walter R. Jiang, Chengyong George |
author_facet | Weiss, Walter R. Jiang, Chengyong George |
author_sort | Weiss, Walter R. |
collection | PubMed |
description | Live attenuated malaria vaccines are more potent than the recombinant protein, bacterial or viral platform vaccines that have been tested, and an attenuated sporozoite vaccine against falciparum malaria is being developed for humans. In mice, attenuated malaria sporozoite vaccines induce CD8(+) T cells that kill parasites developing in the liver. We were curious to know if CD8(+) T cells were also important in protecting primates against malaria. We immunized 9 rhesus monkeys with radiation attenuated Plasmodium knowlesi sporozoites, and found that 5 did not develop blood stage infections after challenge with live sporozoites. We then injected 4 of these protected monkeys with cM-T807, a monoclonal antibody to the CD8 molecule which depletes T cells. The fifth monkey received equivalent doses of normal IgG. In 3 of the 4 monkeys receiving cM-T807 circulating CD8(+) T cells were profoundly depleted. When re-challenged with live sporozoites all 3 of these depleted animals developed blood stage malaria. The fourth monkey receiving cM-T807 retained many circulating CD8(+) T cells. This monkey, and the vaccinated monkey receiving normal IgG, did not develop blood stage malaria at re-challenge with live sporozoites. Animals were treated with antimalarial drugs and rested for 4 months. During this interval CD8(+) T cells re-appeared in the circulation of the depleted monkeys. When all vaccinated animals received a third challenge with live sporozoites, all 5 monkeys were once again protected and did not develop blood stage malaria infections. These data indicate that CD8(+) T cells are important effector cells protecting monkeys against malaria sporozoite infection. We believe that malaria vaccines which induce effector CD8+ T cells in humans will have the best chance of protecting against malaria. |
format | Online Article Text |
id | pubmed-3280278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32802782012-02-21 Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites Weiss, Walter R. Jiang, Chengyong George PLoS One Research Article Live attenuated malaria vaccines are more potent than the recombinant protein, bacterial or viral platform vaccines that have been tested, and an attenuated sporozoite vaccine against falciparum malaria is being developed for humans. In mice, attenuated malaria sporozoite vaccines induce CD8(+) T cells that kill parasites developing in the liver. We were curious to know if CD8(+) T cells were also important in protecting primates against malaria. We immunized 9 rhesus monkeys with radiation attenuated Plasmodium knowlesi sporozoites, and found that 5 did not develop blood stage infections after challenge with live sporozoites. We then injected 4 of these protected monkeys with cM-T807, a monoclonal antibody to the CD8 molecule which depletes T cells. The fifth monkey received equivalent doses of normal IgG. In 3 of the 4 monkeys receiving cM-T807 circulating CD8(+) T cells were profoundly depleted. When re-challenged with live sporozoites all 3 of these depleted animals developed blood stage malaria. The fourth monkey receiving cM-T807 retained many circulating CD8(+) T cells. This monkey, and the vaccinated monkey receiving normal IgG, did not develop blood stage malaria at re-challenge with live sporozoites. Animals were treated with antimalarial drugs and rested for 4 months. During this interval CD8(+) T cells re-appeared in the circulation of the depleted monkeys. When all vaccinated animals received a third challenge with live sporozoites, all 5 monkeys were once again protected and did not develop blood stage malaria infections. These data indicate that CD8(+) T cells are important effector cells protecting monkeys against malaria sporozoite infection. We believe that malaria vaccines which induce effector CD8+ T cells in humans will have the best chance of protecting against malaria. Public Library of Science 2012-02-15 /pmc/articles/PMC3280278/ /pubmed/22355349 http://dx.doi.org/10.1371/journal.pone.0031247 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Weiss, Walter R. Jiang, Chengyong George Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites |
title | Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites |
title_full | Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites |
title_fullStr | Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites |
title_full_unstemmed | Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites |
title_short | Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites |
title_sort | protective cd8+ t lymphocytes in primates immunized with malaria sporozoites |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280278/ https://www.ncbi.nlm.nih.gov/pubmed/22355349 http://dx.doi.org/10.1371/journal.pone.0031247 |
work_keys_str_mv | AT weisswalterr protectivecd8tlymphocytesinprimatesimmunizedwithmalariasporozoites AT jiangchengyonggeorge protectivecd8tlymphocytesinprimatesimmunizedwithmalariasporozoites |