Enhancement of protective efficacy through adenoviral vectored vaccine priming and protein boosting strategy encoding triosephosphate isomerase (SjTPI) against Schistosoma japonicum in mice

Abstract

Background: Schistosomiasis japonica is a zoonotic parasitic disease; developing transmission blocking veterinary vaccines are urgently needed for the prevention and control of schistosomiasis in China. Heterologous prime-boost strategy, a novel vaccination approach, is more effective in enhancing vaccine efficacy against multiple pathogens. In the present study, we established a novel heterologous prime-boost vaccination strategy, the rAdV-SjTPI.opt intramuscular priming and rSjTPI subcutaneous boosting strategy, and evaluated its protective efficacy against Schistosoma japonicum in mice.

Methodology/principal findings: Adenoviral vectored vaccine (rAdV-SjTPI.opt) and recombinant protein vaccine (rSjTPI) were prepared and used in different combinations as vaccines in a mouse model. The specific immune responses and protective efficacies were evaluated. Furthermore, the longevity of protective efficacy was also determined. Results showed that the rAdV-SjTPI.opt priming-rSjTPI boosting strategy elicited higher levels of specific IgG responses and broad-spectrum specific cellular immune responses. The protective efficacy could reach up to nearly 70% and 50% of protection could be observed at 10 weeks after the last immunization in mice.

Conclusions/significance: The rAdV-SjTPI.opt intramuscular priming-rSjTPI subcutaneous boosting vaccination strategy is a novel, highly efficient, and stable approach to developing vaccines against Schistosoma japonicum infections in China.

Fig 1. rSjTPI-specific antibody responses in mice sera induced by Ad vector, rSjTPI, rAdV-SjTPI.opt, rAdV-SjTPI.opt priming-rSjTPI boosting immunized groups, and control group.

(A) IgG responses; (B) IgG titer; (C) IgG1 and IgG2a responses; (D) IgG avidity; each bar represents the mean ± standard deviation (SD). *P<0.05; **P<0.01.

Fig 2. rSjTPI-specific cytokine responses in splenocytes induced by Ad vector, rSjTPI, rAdV-SjTPI.opt, rAdV-SjTPI.opt priming-rSjTPI boosting immunized groups, and control group.

Panels A-F show IL-2, IFN-γ, TNF, IL-6, IL-10, and IL-17A levels, respectively, in splenocyte culture supernatants stimulated with rSjTPI (10 μg/ml) or medium (mock); the splenocytes were also stimulated with rSjTPI (10 μg/ml). Panel G shows the spot counts of IL-4 and IFN-γ secreting cells in each group. Each bar represents the mean ± standard deviation (SD). *P<0.05; **P<0.01.

Fig 3. The single egg granuloma responses in liver induced by Ad vector, rSjTPI, rAdV-SjTPI.opt, and rAdV-SjTPI.opt priming-rSjTPI boosting immunization.

(A) Representative granuloma of each group, induced by a single egg in liver (magnification factor 10×10); (B) Areas of the single egg granuloma in liver. Data is presented as the mean ± standard deviation (SD). *P<0.05; **P<0.01.

Fig 4. rSjTPI-specific IgG responses induced by rAdV-SjTPI.opt priming-rSjTPI (s.c.) boosting strategy at 2, 6, and 10 weeks after the last immunization.

Panel A shows IgG responses and IgG avidity. Panel B shows the IgG titers. Data is presented as the mean ± standard deviation (SD). *P<0.05; **P<0.01.

Fig 5. rSjTPI-specific cytokine responses induced by rAdV-SjTPI.opt priming-rSjTPI boosting strategy at 2, 6, and 10 weeks after the last immunization.

Panels A-F show IL-2, IFN-γ, TNF, IL-6, IL-10, and IL-17A levels, respectively, in splenocyte culture supernatants stimulated with rSjTPI (10 μg/ml) or medium (mock). Data is presented as the mean ± standard deviation (SD). *P<0.05; **P<0.01.