Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver.

Whole malaria sporozoite vaccine regimens are promising new strategies, and some candidates have demonstrated high rates of durable clinical protection associated with memory T cell responses. Little is known about the anatomical distribution of memory T cells following whole sporozoite vaccines, an...

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Main Authors: Sathit Pichyangkul, Michele D Spring, Kosol Yongvanitchit, Utaiwan Kum-Arb, Amporn Limsalakpetch, Rawiwan Im-Erbsin, Ratawan Ubalee, Pattaraporn Vanachayangkul, Edmond J Remarque, Evelina Angov, Philip L Smith, David L Saunders
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5300246?pdf=render
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author Sathit Pichyangkul
Michele D Spring
Kosol Yongvanitchit
Utaiwan Kum-Arb
Amporn Limsalakpetch
Rawiwan Im-Erbsin
Ratawan Ubalee
Pattaraporn Vanachayangkul
Edmond J Remarque
Evelina Angov
Philip L Smith
David L Saunders
author_facet Sathit Pichyangkul
Michele D Spring
Kosol Yongvanitchit
Utaiwan Kum-Arb
Amporn Limsalakpetch
Rawiwan Im-Erbsin
Ratawan Ubalee
Pattaraporn Vanachayangkul
Edmond J Remarque
Evelina Angov
Philip L Smith
David L Saunders
author_sort Sathit Pichyangkul
collection DOAJ
description Whole malaria sporozoite vaccine regimens are promising new strategies, and some candidates have demonstrated high rates of durable clinical protection associated with memory T cell responses. Little is known about the anatomical distribution of memory T cells following whole sporozoite vaccines, and immunization of nonhuman primates can be used as a relevant model for humans. We conducted a chemoprophylaxis with sporozoite (CPS) immunization in P. knowlesi rhesus monkeys and challenged via mosquito bites. Half of CPS immunized animals developed complete protection, with a marked delay in parasitemia demonstrated in the other half. Antibody responses to whole sporozoites, CSP, and AMA1, but not CelTOS were detected. Peripheral blood T cell responses to whole sporozoites, but not CSP and AMA1 peptides were observed. Unlike peripheral blood, there was a high frequency of sporozoite-specific memory T cells observed in the liver and bone marrow. Interestingly, sporozoite-specific CD4+ and CD8+ memory T cells in the liver highly expressed chemokine receptors CCR5 and CXCR6, both of which are known for liver sinusoid homing. The majority of liver sporozoite-specific memory T cells expressed CD69, a phenotypic marker of tissue-resident memory (TRM) cells, which are well positioned to rapidly control liver-stage infection. Vaccine strategies that aim to elicit large number of liver TRM cells may efficiently increase the efficacy and durability of response against pre-erythrocytic parasites.
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spelling doaj.art-7f661793fdd74de08c780c59b59ab2a82022-12-21T19:29:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017182610.1371/journal.pone.0171826Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver.Sathit PichyangkulMichele D SpringKosol YongvanitchitUtaiwan Kum-ArbAmporn LimsalakpetchRawiwan Im-ErbsinRatawan UbaleePattaraporn VanachayangkulEdmond J RemarqueEvelina AngovPhilip L SmithDavid L SaundersWhole malaria sporozoite vaccine regimens are promising new strategies, and some candidates have demonstrated high rates of durable clinical protection associated with memory T cell responses. Little is known about the anatomical distribution of memory T cells following whole sporozoite vaccines, and immunization of nonhuman primates can be used as a relevant model for humans. We conducted a chemoprophylaxis with sporozoite (CPS) immunization in P. knowlesi rhesus monkeys and challenged via mosquito bites. Half of CPS immunized animals developed complete protection, with a marked delay in parasitemia demonstrated in the other half. Antibody responses to whole sporozoites, CSP, and AMA1, but not CelTOS were detected. Peripheral blood T cell responses to whole sporozoites, but not CSP and AMA1 peptides were observed. Unlike peripheral blood, there was a high frequency of sporozoite-specific memory T cells observed in the liver and bone marrow. Interestingly, sporozoite-specific CD4+ and CD8+ memory T cells in the liver highly expressed chemokine receptors CCR5 and CXCR6, both of which are known for liver sinusoid homing. The majority of liver sporozoite-specific memory T cells expressed CD69, a phenotypic marker of tissue-resident memory (TRM) cells, which are well positioned to rapidly control liver-stage infection. Vaccine strategies that aim to elicit large number of liver TRM cells may efficiently increase the efficacy and durability of response against pre-erythrocytic parasites.http://europepmc.org/articles/PMC5300246?pdf=render
spellingShingle Sathit Pichyangkul
Michele D Spring
Kosol Yongvanitchit
Utaiwan Kum-Arb
Amporn Limsalakpetch
Rawiwan Im-Erbsin
Ratawan Ubalee
Pattaraporn Vanachayangkul
Edmond J Remarque
Evelina Angov
Philip L Smith
David L Saunders
Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver.
PLoS ONE
title Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver.
title_full Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver.
title_fullStr Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver.
title_full_unstemmed Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver.
title_short Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver.
title_sort chemoprophylaxis with sporozoite immunization in p knowlesi rhesus monkeys confers protection and elicits sporozoite specific memory t cells in the liver
url http://europepmc.org/articles/PMC5300246?pdf=render
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