Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model

The malaria parasite Plasmodium vivax remains a major global public health challenge, and no vaccine is approved for use in humans. Here, we assessed whether P. vivax strain-transcendent immunity can be achieved by repeated infection in Aotus monkeys. Sterile immunity was achieved after two homologo...

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Main Authors: Obaldía, Nicanor, Da Silva Filho, Joao Luiz, Núñez, Marlon, Glass, Katherine A., Oulton, Tate, Achcar, Fiona, Wirjanata, Grennady, Duraisingh, Manoj, Felgner, Philip, Tetteh, Kevin Ka, Bozdech, Zbynek, Otto, Thomas D., Marti, Matthias
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2024
Subjects:
Online Access:https://hdl.handle.net/10356/178486
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author Obaldía, Nicanor
Da Silva Filho, Joao Luiz
Núñez, Marlon
Glass, Katherine A.
Oulton, Tate
Achcar, Fiona
Wirjanata, Grennady
Duraisingh, Manoj
Felgner, Philip
Tetteh, Kevin Ka
Bozdech, Zbynek
Otto, Thomas D.
Marti, Matthias
author2 School of Biological Sciences
author_facet School of Biological Sciences
Obaldía, Nicanor
Da Silva Filho, Joao Luiz
Núñez, Marlon
Glass, Katherine A.
Oulton, Tate
Achcar, Fiona
Wirjanata, Grennady
Duraisingh, Manoj
Felgner, Philip
Tetteh, Kevin Ka
Bozdech, Zbynek
Otto, Thomas D.
Marti, Matthias
author_sort Obaldía, Nicanor
collection NTU
description The malaria parasite Plasmodium vivax remains a major global public health challenge, and no vaccine is approved for use in humans. Here, we assessed whether P. vivax strain-transcendent immunity can be achieved by repeated infection in Aotus monkeys. Sterile immunity was achieved after two homologous infections, whereas subsequent heterologous challenge provided only partial protection. IgG levels based on P. vivax lysate ELISA and protein microarray increased with repeated infections and correlated with the level of homologous protection. Parasite transcriptional profiles provided no evidence of major antigenic switching upon homologous or heterologous challenge. However, we observed significant sequence diversity and transcriptional differences in the P. vivax core gene repertoire between the two strains used in the study, suggesting that partial protection upon heterologous challenge is due to molecular differences between strains rather than immune evasion by antigenic switching. Our study demonstrates that sterile immunity against P. vivax can be achieved by repeated homologous blood stage infection in Aotus monkeys, thus providing a benchmark to test the efficacy of candidate blood stage P. vivax malaria vaccines.
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spelling ntu-10356/1784862024-06-24T15:32:04Z Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model Obaldía, Nicanor Da Silva Filho, Joao Luiz Núñez, Marlon Glass, Katherine A. Oulton, Tate Achcar, Fiona Wirjanata, Grennady Duraisingh, Manoj Felgner, Philip Tetteh, Kevin Ka Bozdech, Zbynek Otto, Thomas D. Marti, Matthias School of Biological Sciences Medicine, Health and Life Sciences Aotidae Malaria The malaria parasite Plasmodium vivax remains a major global public health challenge, and no vaccine is approved for use in humans. Here, we assessed whether P. vivax strain-transcendent immunity can be achieved by repeated infection in Aotus monkeys. Sterile immunity was achieved after two homologous infections, whereas subsequent heterologous challenge provided only partial protection. IgG levels based on P. vivax lysate ELISA and protein microarray increased with repeated infections and correlated with the level of homologous protection. Parasite transcriptional profiles provided no evidence of major antigenic switching upon homologous or heterologous challenge. However, we observed significant sequence diversity and transcriptional differences in the P. vivax core gene repertoire between the two strains used in the study, suggesting that partial protection upon heterologous challenge is due to molecular differences between strains rather than immune evasion by antigenic switching. Our study demonstrates that sterile immunity against P. vivax can be achieved by repeated homologous blood stage infection in Aotus monkeys, thus providing a benchmark to test the efficacy of candidate blood stage P. vivax malaria vaccines. Published version Funding for this study was provided in part by core funds from the Gorgas Memorial Institute of Health Studies and the Sistema Nacional de Investigación de Panamá, SENACYT-SNI awarded to N Obaldía, Panamá, Panamá. This work was also supported by Royal Society Wolfson Research Merit Award (to M Marti) and Wellcome Trust Center Award 104111 (to F Achcar, JL Da Silva Filho, TD Otto, and M Marti). 2024-06-24T04:56:42Z 2024-06-24T04:56:42Z 2024 Journal Article Obaldía, N., Da Silva Filho, J. L., Núñez, M., Glass, K. A., Oulton, T., Achcar, F., Wirjanata, G., Duraisingh, M., Felgner, P., Tetteh, K. K., Bozdech, Z., Otto, T. D. & Marti, M. (2024). Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model. Life Science Alliance, 7(3), e202302524-. https://dx.doi.org/10.26508/lsa.202302524 2575-1077 https://hdl.handle.net/10356/178486 10.26508/lsa.202302524 38158220 2-s2.0-85181205207 3 7 e202302524 en Life Science Alliance © 2023 Obaldía et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). application/pdf
spellingShingle Medicine, Health and Life Sciences
Aotidae
Malaria
Obaldía, Nicanor
Da Silva Filho, Joao Luiz
Núñez, Marlon
Glass, Katherine A.
Oulton, Tate
Achcar, Fiona
Wirjanata, Grennady
Duraisingh, Manoj
Felgner, Philip
Tetteh, Kevin Ka
Bozdech, Zbynek
Otto, Thomas D.
Marti, Matthias
Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model
title Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model
title_full Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model
title_fullStr Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model
title_full_unstemmed Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model
title_short Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model
title_sort sterile protection against p vivax malaria by repeated blood stage infection in the aotus monkey model
topic Medicine, Health and Life Sciences
Aotidae
Malaria
url https://hdl.handle.net/10356/178486
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