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Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria

BACKGROUND: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the co...

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Autores principales: Bell, Griffin J, Gyaase, Stephaney, Goel, Varun, Adu, Bright, Mensah, Benedicta, Essone, Paulin, Dosoo, David, Osei, Musah, Niare, Karamoko, Wiru, Kenneth, Brandt, Katerina, Emch, Michael, Ghansah, Anita, Asante, Kwaku Poku, Mvalo, Tisungane, Agnandji, Selidji Todagbe, Juliano, Jonathan J, Bailey, Jeffrey A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594884/
https://www.ncbi.nlm.nih.gov/pubmed/37872492
http://dx.doi.org/10.1186/s12879-023-08699-7
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author Bell, Griffin J
Gyaase, Stephaney
Goel, Varun
Adu, Bright
Mensah, Benedicta
Essone, Paulin
Dosoo, David
Osei, Musah
Niare, Karamoko
Wiru, Kenneth
Brandt, Katerina
Emch, Michael
Ghansah, Anita
Asante, Kwaku Poku
Mvalo, Tisungane
Agnandji, Selidji Todagbe
Juliano, Jonathan J
Bailey, Jeffrey A
author_facet Bell, Griffin J
Gyaase, Stephaney
Goel, Varun
Adu, Bright
Mensah, Benedicta
Essone, Paulin
Dosoo, David
Osei, Musah
Niare, Karamoko
Wiru, Kenneth
Brandt, Katerina
Emch, Michael
Ghansah, Anita
Asante, Kwaku Poku
Mvalo, Tisungane
Agnandji, Selidji Todagbe
Juliano, Jonathan J
Bailey, Jeffrey A
author_sort Bell, Griffin J
collection PubMed
description BACKGROUND: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group. METHODS: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009–2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01. RESULTS: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series. CONCLUSIONS: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-023-08699-7.
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spelling pubmed-105948842023-10-25 Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria Bell, Griffin J Gyaase, Stephaney Goel, Varun Adu, Bright Mensah, Benedicta Essone, Paulin Dosoo, David Osei, Musah Niare, Karamoko Wiru, Kenneth Brandt, Katerina Emch, Michael Ghansah, Anita Asante, Kwaku Poku Mvalo, Tisungane Agnandji, Selidji Todagbe Juliano, Jonathan J Bailey, Jeffrey A BMC Infect Dis Research BACKGROUND: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group. METHODS: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009–2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01. RESULTS: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series. CONCLUSIONS: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-023-08699-7. BioMed Central 2023-10-23 /pmc/articles/PMC10594884/ /pubmed/37872492 http://dx.doi.org/10.1186/s12879-023-08699-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Bell, Griffin J
Gyaase, Stephaney
Goel, Varun
Adu, Bright
Mensah, Benedicta
Essone, Paulin
Dosoo, David
Osei, Musah
Niare, Karamoko
Wiru, Kenneth
Brandt, Katerina
Emch, Michael
Ghansah, Anita
Asante, Kwaku Poku
Mvalo, Tisungane
Agnandji, Selidji Todagbe
Juliano, Jonathan J
Bailey, Jeffrey A
Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
title Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
title_full Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
title_fullStr Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
title_full_unstemmed Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
title_short Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
title_sort background malaria incidence and parasitemia during the three-dose rts,s/as01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594884/
https://www.ncbi.nlm.nih.gov/pubmed/37872492
http://dx.doi.org/10.1186/s12879-023-08699-7
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