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RTS,S/AS02A Malaria Vaccine Does Not Induce Parasite CSP T Cell Epitope Selection and Reduces Multiplicity of Infection
OBJECTIVE: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in chi...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488895/ https://www.ncbi.nlm.nih.gov/pubmed/16871327 http://dx.doi.org/10.1371/journal.pctr.0010005 |
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author | Enosse, Sonia Dobaño, Carlota Quelhas, Diana Aponte, John J Lievens, Marc Leach, Amanda Sacarlal, Jahit Greenwood, Brian Milman, Jessica Dubovsky, Filip Cohen, Joe Thompson, Ricardo Ballou, W. Ripley Alonso, Pedro L Conway, David J Sutherland, Colin J |
author_facet | Enosse, Sonia Dobaño, Carlota Quelhas, Diana Aponte, John J Lievens, Marc Leach, Amanda Sacarlal, Jahit Greenwood, Brian Milman, Jessica Dubovsky, Filip Cohen, Joe Thompson, Ricardo Ballou, W. Ripley Alonso, Pedro L Conway, David J Sutherland, Colin J |
author_sort | Enosse, Sonia |
collection | PubMed |
description | OBJECTIVE: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccine demonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. DESIGN: P. falciparum DNA from isolates collected during the trial was used for genotype studies. SETTING: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. PARTICIPANTS: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. OUTCOME: Divergence of DNA sequence encoding the CSP T cell–epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. RESULTS: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at study month 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p = 0.035, p = 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p = 0.478). CONCLUSIONS: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections. |
format | Text |
id | pubmed-1488895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-14888952006-07-25 RTS,S/AS02A Malaria Vaccine Does Not Induce Parasite CSP T Cell Epitope Selection and Reduces Multiplicity of Infection Enosse, Sonia Dobaño, Carlota Quelhas, Diana Aponte, John J Lievens, Marc Leach, Amanda Sacarlal, Jahit Greenwood, Brian Milman, Jessica Dubovsky, Filip Cohen, Joe Thompson, Ricardo Ballou, W. Ripley Alonso, Pedro L Conway, David J Sutherland, Colin J PLoS Clin Trials Research Article OBJECTIVE: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccine demonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. DESIGN: P. falciparum DNA from isolates collected during the trial was used for genotype studies. SETTING: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. PARTICIPANTS: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. OUTCOME: Divergence of DNA sequence encoding the CSP T cell–epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. RESULTS: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at study month 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p = 0.035, p = 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p = 0.478). CONCLUSIONS: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections. Public Library of Science 2006-05-19 /pmc/articles/PMC1488895/ /pubmed/16871327 http://dx.doi.org/10.1371/journal.pctr.0010005 Text en © 2006 Enosse et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Enosse, Sonia Dobaño, Carlota Quelhas, Diana Aponte, John J Lievens, Marc Leach, Amanda Sacarlal, Jahit Greenwood, Brian Milman, Jessica Dubovsky, Filip Cohen, Joe Thompson, Ricardo Ballou, W. Ripley Alonso, Pedro L Conway, David J Sutherland, Colin J RTS,S/AS02A Malaria Vaccine Does Not Induce Parasite CSP T Cell Epitope Selection and Reduces Multiplicity of Infection |
title | RTS,S/AS02A Malaria Vaccine Does Not Induce Parasite CSP T Cell Epitope Selection and Reduces Multiplicity of Infection |
title_full | RTS,S/AS02A Malaria Vaccine Does Not Induce Parasite CSP T Cell Epitope Selection and Reduces Multiplicity of Infection |
title_fullStr | RTS,S/AS02A Malaria Vaccine Does Not Induce Parasite CSP T Cell Epitope Selection and Reduces Multiplicity of Infection |
title_full_unstemmed | RTS,S/AS02A Malaria Vaccine Does Not Induce Parasite CSP T Cell Epitope Selection and Reduces Multiplicity of Infection |
title_short | RTS,S/AS02A Malaria Vaccine Does Not Induce Parasite CSP T Cell Epitope Selection and Reduces Multiplicity of Infection |
title_sort | rts,s/as02a malaria vaccine does not induce parasite csp t cell epitope selection and reduces multiplicity of infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488895/ https://www.ncbi.nlm.nih.gov/pubmed/16871327 http://dx.doi.org/10.1371/journal.pctr.0010005 |
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