Infectious sporozoite challenge modulates radiation attenuated sporozoite vaccine–induced memory CD8+ T cells for better survival characteristics

Abstract

Radiation attenuated sporozoite (RAS), a whole-parasite vaccine approach, provides sterile protection against malaria. However, RAS immunization does not confer protection for long, and that has been correlated with the waning parasite–induced memory CD8+ T-cell responses. Interestingly, an intermittent infectious (wild type) sporozoite challenge to the RAS-vaccinated mice lengthened the protection period from 6 to 18 months. Herein, we have studied the changes induced by the infectious sporozoites in RAS-induced memory CD8+ T cells for conferring lengthened protection. We observed that the infectious sporozoite challenge boosted the frequency of foreign antigen–experienced memory CD8+ T cells. In those CD8+ T cells, it has reduced the Annexin-V reactivity, raised Bcl-2 expression, and also more cells undergo homeostatic proliferation (Ki-67+). It has also scaled down the frequency of Nur77 and CX3CR1 high expressing cells in those memory CD8+ T-cell populations which we further correlated with better survival signals.