{gamma}{delta} T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations [IMMUNOTHERAPY AND VACCINES]

Whole-sporozoite vaccines confer sterilizing immunity to malaria-naive individuals by unknown mechanisms. In the first PfSPZ Vaccine trial ever in a malaria-endemic population, V2 T cells were significantly elevated and V9/V2 transcripts ranked as the most upregulated in vaccinees who were protected from Plasmodium falciparum infection. In a mouse model, absence of T cells during vaccination impaired protective CD8 T cell responses and ablated sterile protection. T cells were not required for circumsporozoite protein–specific Ab responses, and T cell depletion before infectious challenge did not ablate protection. T cells alone were insufficient to induce protection and required the presence of CD8α⁺ dendritic cells. In the absence of T cells, CD8α⁺ dendritic cells did not accumulate in the livers of vaccinated mice. Altogether, our results show that T cells were essential for the induction of sterile immunity during whole-organism vaccination.

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