Induction of a Th1-Type Polyfunctional T-Cell Response by the Four-segmented Rift Valley Fever Candidate Vaccine in Humans.

BACKGROUND

Rift Valley fever virus (RVFV) is a mosquito-borne virus that affects livestock and humans. The 4-segmented live-attenuated human vaccine candidate hRVFV-4s has shown a strong safety profile and excellent tolerability in healthy adults during a first-in-human clinical trial, while also eliciting both neutralizing antibody and T-cell responses. Recognizing the critical role of cellular immunity in vaccine-induced protection and immune durability, this study aimed to comprehensively characterize the cytokine secretion profile, the antigen-specific breadth of RVFV-specific T-cell responses and memory T-cell formation, elicited by a single dose of hRVFV-4s, up to 6 months post-vaccination.

METHODS

Peripheral blood mononuclear cells collected during the first-in-human clinical trial at 0, 7, 14, and 180 days post hRVFV-4s vaccination were analyzed for RVFV-specific T-cell responses using multiparametric flow cytometry and multiplex cytokine detection assays.

RESULTS

A strong N-specific peripheral CD4+ and CD8+ T-cell response was detected among vaccinees, accompanied by Gn- and Gc-specific T cells, albeit the latter at comparatively lower frequencies. These responses were mediated by polyfunctional CD4+ and CD8+ T cells, which were detectable as early as at 2 weeks post-vaccination. The RVFV-specific T-cells were primarily of the effector memory phenotype and demonstrated cytokine secretion profiles characteristic of a T helper 1 (Th1)-type.

CONCLUSIONS

This study demonstrates that the cell-mediated immune response induced by a single dose of the hRVFV-4s vaccine is characterized by robust, virus-specific Th1-type CD4+ and CD8+ T-cell response. Together with previously reported virus-neutralizing antibody responses, these coordinated immune responses are expected to contribute to vaccine-mediated protection.