Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine

Abstract Background To gain a deeper understanding of protective immunity against relapsing malaria, this study examined sporozoite-specific T cell responses induced by a chemoprophylaxis with sporozoite (CPS) immunization in a relapsing Plasmodium cynomolgi rhesus macaque model. Methods The animals...

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Main Authors: Kosol Yongvanitchit, Utaiwan Kum-Arb, Amporn Limsalakpetch, Rawiwan Im-Erbsin, Ratawan Ubalee, Michele D. Spring, Brian A. Vesely, Norman Waters, Sathit Pichyangkul
Format: Article
Language:English
Published: BMC 2024-04-01
Series:Malaria Journal
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Online Access:https://doi.org/10.1186/s12936-024-04933-y
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author Kosol Yongvanitchit
Utaiwan Kum-Arb
Amporn Limsalakpetch
Rawiwan Im-Erbsin
Ratawan Ubalee
Michele D. Spring
Brian A. Vesely
Norman Waters
Sathit Pichyangkul
author_facet Kosol Yongvanitchit
Utaiwan Kum-Arb
Amporn Limsalakpetch
Rawiwan Im-Erbsin
Ratawan Ubalee
Michele D. Spring
Brian A. Vesely
Norman Waters
Sathit Pichyangkul
author_sort Kosol Yongvanitchit
collection DOAJ
description Abstract Background To gain a deeper understanding of protective immunity against relapsing malaria, this study examined sporozoite-specific T cell responses induced by a chemoprophylaxis with sporozoite (CPS) immunization in a relapsing Plasmodium cynomolgi rhesus macaque model. Methods The animals received three CPS immunizations with P. cynomolgi sporozoites, administered by mosquito bite, while under two anti-malarial drug regimens. Group 1 (n = 6) received artesunate/chloroquine (AS/CQ) followed by a radical cure with CQ plus primaquine (PQ). Group 2 (n = 6) received atovaquone-proguanil (AP) followed by PQ. After the final immunization, the animals were challenged with intravenous injection of 104 P. cynomolgi sporozoites, the dose that induced reliable infection and relapse rate. These animals, along with control animals (n = 6), were monitored for primary infection and subsequent relapses. Immunogenicity blood draws were done after each of the three CPS session, before and after the challenge, with liver, spleen and bone marrow sampling and analysis done after the challenge. Results Group 2 animals demonstrated superior protection, with two achieving protection and two experiencing partial protection, while only one animal in group 1 had partial protection. These animals displayed high sporozoite-specific IFN-γ T cell responses in the liver, spleen, and bone marrow after the challenge with one protected animal having the highest frequency of IFN-γ+ CD8+, IFN-γ+ CD4+, and IFN-γ+ γδ T cells in the liver. Partially protected animals also demonstrated a relatively high frequency of IFN-γ+ CD8+, IFN-γ+ CD4+, and IFN-γ+ γδ T cells in the liver. It is important to highlight that the second animal in group 2, which experienced protection, exhibited deficient sporozoite-specific T cell responses in the liver while displaying average to high T cell responses in the spleen and bone marrow. Conclusions This research supports the notion that local liver T cell immunity plays a crucial role in defending against liver-stage infection. Nevertheless, there is an instance where protection occurs independently of T cell responses in the liver, suggesting the involvement of the liver's innate immunity. The relapsing P. cynomolgi rhesus macaque model holds promise for informing the development of vaccines against relapsing P. vivax.
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spelling doaj.art-40f8354ee28a4652814b67e54051f7b82024-04-21T11:09:07ZengBMCMalaria Journal1475-28752024-04-0123111310.1186/s12936-024-04933-ySuperior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquineKosol Yongvanitchit0Utaiwan Kum-Arb1Amporn Limsalakpetch2Rawiwan Im-Erbsin3Ratawan Ubalee4Michele D. Spring5Brian A. Vesely6Norman Waters7Sathit Pichyangkul8Armed Forces Research Institute of Medical Sciences (AFRIMS)Armed Forces Research Institute of Medical Sciences (AFRIMS)Armed Forces Research Institute of Medical Sciences (AFRIMS)Armed Forces Research Institute of Medical Sciences (AFRIMS)Armed Forces Research Institute of Medical Sciences (AFRIMS)Armed Forces Research Institute of Medical Sciences (AFRIMS)Armed Forces Research Institute of Medical Sciences (AFRIMS)Armed Forces Research Institute of Medical Sciences (AFRIMS)Armed Forces Research Institute of Medical Sciences (AFRIMS)Abstract Background To gain a deeper understanding of protective immunity against relapsing malaria, this study examined sporozoite-specific T cell responses induced by a chemoprophylaxis with sporozoite (CPS) immunization in a relapsing Plasmodium cynomolgi rhesus macaque model. Methods The animals received three CPS immunizations with P. cynomolgi sporozoites, administered by mosquito bite, while under two anti-malarial drug regimens. Group 1 (n = 6) received artesunate/chloroquine (AS/CQ) followed by a radical cure with CQ plus primaquine (PQ). Group 2 (n = 6) received atovaquone-proguanil (AP) followed by PQ. After the final immunization, the animals were challenged with intravenous injection of 104 P. cynomolgi sporozoites, the dose that induced reliable infection and relapse rate. These animals, along with control animals (n = 6), were monitored for primary infection and subsequent relapses. Immunogenicity blood draws were done after each of the three CPS session, before and after the challenge, with liver, spleen and bone marrow sampling and analysis done after the challenge. Results Group 2 animals demonstrated superior protection, with two achieving protection and two experiencing partial protection, while only one animal in group 1 had partial protection. These animals displayed high sporozoite-specific IFN-γ T cell responses in the liver, spleen, and bone marrow after the challenge with one protected animal having the highest frequency of IFN-γ+ CD8+, IFN-γ+ CD4+, and IFN-γ+ γδ T cells in the liver. Partially protected animals also demonstrated a relatively high frequency of IFN-γ+ CD8+, IFN-γ+ CD4+, and IFN-γ+ γδ T cells in the liver. It is important to highlight that the second animal in group 2, which experienced protection, exhibited deficient sporozoite-specific T cell responses in the liver while displaying average to high T cell responses in the spleen and bone marrow. Conclusions This research supports the notion that local liver T cell immunity plays a crucial role in defending against liver-stage infection. Nevertheless, there is an instance where protection occurs independently of T cell responses in the liver, suggesting the involvement of the liver's innate immunity. The relapsing P. cynomolgi rhesus macaque model holds promise for informing the development of vaccines against relapsing P. vivax.https://doi.org/10.1186/s12936-024-04933-yRelapsing Plasmodium cynomolgi rhesus macaque modelChemoprophylaxis with sporozoite immunizationAtovaquone-proguanilSporozoite-specific T cell responses
spellingShingle Kosol Yongvanitchit
Utaiwan Kum-Arb
Amporn Limsalakpetch
Rawiwan Im-Erbsin
Ratawan Ubalee
Michele D. Spring
Brian A. Vesely
Norman Waters
Sathit Pichyangkul
Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine
Malaria Journal
Relapsing Plasmodium cynomolgi rhesus macaque model
Chemoprophylaxis with sporozoite immunization
Atovaquone-proguanil
Sporozoite-specific T cell responses
title Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine
title_full Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine
title_fullStr Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine
title_full_unstemmed Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine
title_short Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine
title_sort superior protection in a relapsing plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone proguanil followed by primaquine
topic Relapsing Plasmodium cynomolgi rhesus macaque model
Chemoprophylaxis with sporozoite immunization
Atovaquone-proguanil
Sporozoite-specific T cell responses
url https://doi.org/10.1186/s12936-024-04933-y
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