Cellular and Humoral Immunity to Ebola Zaire Glycoprotein and Viral Vector Proteins Following Immunization with Recombinant Vesicular Stomatitis Virus-Based Ebola Vaccine (rVSVΔG-EBOV-GP)

Abstract

AbstractWhile effective at preventing Zaire ebolavirus (EBOV) disease, cellular immunity to EBOV and vector-directed immunity elicited by the recombinant vesicular stomatitis virus expressing Ebola glycoprotein (rVSVΔG-EBOV-GP) vaccine remains poorly understood. Sera and peripheral blood mononuclear cells were collected from 32 participants enrolled in a prospective multicenter study [ClinicalTrials.govNCT02788227] before vaccination and up to six months post-vaccination. IgM and IgG antibodies, IgG-producing memory B cells, and T cell reactivity to EBOV glycoprotein, vesicular stomatitis virus-Indiana strain (VSV-I) matrix protein, and VSV-I nucleoprotein were measured using ELISA, ELISpot, and intracellular cytokine staining, respectively. Eleven participants previously received a different investigational Ebola vaccine. All participants met positivity criteria for IgG antibodies to, and circulating IgG-producing memory B cells to, EBOV glycoprotein following rVSVΔG-EBOV-GP vaccination. Transient IgM and IgG antibody responses to VSV-I matrix protein (n=1/32 and n=0/32, respectively) and nucleoprotein (n=2/32 and n=1/32, respectively) were infrequently detected, as were IgG-producing memory B cells recognizing VSV-I matrix protein (n=3/31) and nucleoprotein (n=2/31). CD4+ and CD8+ T cell responses to EBOV glycoprotein were present in 15/32 and 19/32 participants at baseline and in 32/32 and 23/32 participants one month post-vaccination, respectively. CD4+ and CD8+ T cell responses to VSV-I matrix protein (n=17/32 and n=16/32, respectively) and VSV-I nucleoprotein (n=23/32 for both CD4+ and CD8+ responses) were common post-vaccination. T cell responses were predominantly mono-cytokine, except CD8+ responses to EBOV glycoprotein among heterologous Ebola vaccine-experienced participants and CD8+ responses to VSV-I nucleoprotein. Overall, rVSVΔG-EBOV-GP elicits robust humoral and memory B cell responses to EBOV glycoprotein in both Ebola vaccine-naïve and heterologous Ebola vaccine-experienced individuals and can generate vector-directed T cell immunity. Further research is needed to understand the significance of pre-existing vector-directed immunity on responses to booster doses of rVSVΔG-EBOV-GP and other rVSV-vectored vaccines.