Intranasal parainfluenza virus type 5 (PIV5)-vectored RSV vaccine is safe and immunogenic in healthy adults in a phase 1 clinical study

Abstract

Respiratory syncytial virus (RSV) can lead to serious disease in infants, and no approved RSV vaccine is available for infants. This first in-human clinical trial evaluated a single dose of BLB201, a PIV5-vectored RSV vaccine administrated via intranasal route, for safety and immunogenicity in RSV-seropositive healthy adults (33 to 75 years old). No severe adverse events (SAEs) were reported. Solicited local and systemic AEs were reported by <50% of participants and were mostly mild in intensity. Vaccine virus shedding was detected in 17% of participants. Nasal RSV-specific immunoglobulin A responses were detected in 48%, the highest level observed in adults among all intranasal RSV vaccines evaluated in humans. RSV-neutralizing antibodies titers in serum rose ≥1.5-fold. Peripheral blood RSV F-specific CD4+ and CD8+ T cells increased from ≤0.06% at baseline to ≥0.26 and 0.4% after vaccination, respectively, in >93% participants. The safety and immunogenicity profile of BLB201 in RSV-seropositive adults supports the further clinical development of BLB201.

Figures

Fig. 1.. Vaccine-virus shedding. PIV5 viral genomic RNA detection by RTqPCR in individual BLB201 recipients at days 8 and 15.

The dotted line indicates the LOD at 4.6 log10 copies/ml.

Fig. 2.. Serum RSV-specific Ab titers before and after vaccination.

(A) RSV nAbs by microneutralization assay and (B) F-specific RSV IgA Abs and (C) F-specific IgG Abs by enzyme-linked immunosorbent assay (ELISA). Individual log2 titers and mean log2 titers with the respective SDs (error bars) at days 1, 15, and 29 by age group are shown in the graphs in the left column, and GMFRs from baseline on days 15 and 29 by age group are shown in the graphs in the right column. *P < 0.05, **P < 0.01, and ***P < 0.001 by Wilcoxon test.

Fig. 3.. Serum PIV5 Ab titers before and after vaccination.

(A) PIV5 nAbs by microneutralization assay and (B) PIV5-specific RSV IgG Abs by ELISA. Individual log2 titers, and mean log2 titers with the respective SDs (error bars) at days 1, 15, and 29 by age group are shown in the graphs in the left column, and GMFRs from baseline on days 15 and 29 by age group are shown in the graphs in the right column. *P < 0.05, **P < 0.01, and ***P < 0.001 by Wilcoxon test.

Fig. 4.. Nasal IgA Ab titers before and after vaccination.

F-specific RSV IgA Abs by ELISA. Individual log2 titers, and mean log2 titers with the respective SDs (error bars) at days 1, 15, and 29 by age group are shown in the graphs in (A), and GMFRs from baseline on days 15 and 29 by age group are shown in the graphs in (B).

Fig. 5.. RSV F–specific CD4+ and CD8+ T cell frequencies per million PBMCs (by percentage) before and after vaccination.

(A) Percentages of CD4+ T cells (top graphs) and CD8+ T cells (bottom graphs) by age group on days 1, 15, and 29 for each individual (represented by symbols and contiguous line) by expression of the indicated immune marker. (B) Mean percentages of CD4+ T cells (left graphs) and CD8+ T cells (right graphs) by age group on days 1, 15, and 29 by expression of the indicated TH1/cytotoxic marker combinations (IFN-γ, TNF-α, and CD107a) represented in stacked histograms. (C) GMFRs from baseline on days 15 and 29 by age group for CD4+ and CD8+ T cells. (D) Pie chart representations of the proportions of F-specific CD4+ and CD8+ T cells expressing one, two, or three TH1/cytotoxic markers (IFN-γ, TNF-α, and CD107a) at days 15 and 29 in groups 1 and 2. *P < 0.05, **P < 0.01, and ***P < 0.001. ns, not significant.