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, 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.
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Sathit
http://orcid.org/0000-0002-9149-3351
S
Pichyangkul
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Michele D
MD
Spring
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Kosol
K
Yongvanitchit
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Utaiwan
U
Kum-Arb
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Amporn
A
Limsalakpetch
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Rawiwan
R
Im-Erbsin
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Ratawan
R
Ubalee
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Pattaraporn
P
Vanachayangkul
Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Edmond J
EJ
Remarque
Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Evelina
E
Angov
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Philip L
PL
Smith
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
David L
DL
Saunders
D000818:Animals; D000852:Anopheles / Q000469:parasitology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018890:Chemoprevention / Q000379:methods*; D007114:Immunization / Q000379:methods*; D007156:Immunologic Memory; D008099:Liver / Q000276:immunology*; D008253:Macaca mulatta; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D010961:Plasmodium / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D034101:Sporozoites / Q000276:immunology*