Long term protection after immunization with P. berghei sporozoites correlates with sustained IFNγ responses of hepatic CD8+ memory T cells.

PloS One
Krystelle Nganou-MakamdopRobert W Sauerwein

Abstract

Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS) arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS), resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (T(EM)) CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ T(EM) cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r(2) = 0.60, p<0.0001). The reducing IFNγ response by hepatic memory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against mal...Continue Reading

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Citations

Sep 6, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Franziska HentzschelDirk Grimm
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Jan 12, 2021·Expert Review of Vaccines·Reshma J NevagiDanielle I Stanisic
Jul 2, 2021·Chemical Reviews·Kamalakannan VijayanAlexis Kaushansky

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Methods Mentioned

BETA
flow cytometry
PMA
flow-cytometry
ELISA
dissection

Software Mentioned

PRISM
FlowJo

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