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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Public Library of Science (PLoS)
2017-01-01
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| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171826&type=printable |
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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. |
| format | Article |
| id | doaj-art-7f661793fdd74de08c780c59b59ab2a8 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7f661793fdd74de08c780c59b59ab2a82025-08-20T03:12:50ZengPublic 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171826&type=printable |
| 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 | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171826&type=printable |
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