Abstract
BackgroundIn China, schistosomiasis japonica is a predominant zoonotic disease, and animal reservoir hosts in the environment largely sustain infections. The development of transmission-blocking veterinary vaccines is urgently needed for the prevention and efficient control of schistosomiasis. Heterologous prime-boost strategy is more effective than traditional vaccination and homologous prime-boost strategies against multiple pathogens infection. In the present study, to further improve protective efficacy, we immunized mice with three types of heterologous prime-boost combinations based on our previously constructed vaccines that encode triosphate isomerase of Schistosoma japonicum, tested the specific immune responses, and evaluated the protective efficacy through challenge infection in mice.MethodsDNA vaccine (pcDNA3.1-SjTPI.opt), adenoviral vectored vaccine (rAdV-SjTPI.opt), and recombinant protein vaccine (rSjTPI) were prepared and three types of heterologous prime-boost combinations, including DNA i.m. priming-rAdV i.m. boosting, rAdV i.m. priming-rAdV s.c. boosting, and rAdV i.m. priming-rSjTPI boosting strategies, were carried out. The specific immune responses and protective efficacies were evaluated in BALB/c miceResultsResults show that different immune profiles and various levels of protective efficacy were elicited by using different heterologous prime-boost combinations. A synergistic effect was observed using the DNA i.m. priming-rAdV i.m. boosting strategy; however, its protective efficacy was similar to that of rAdV i.m. immunization. Conversely, an antagonistic effect was generated by using the rAd i.m. priming-s.c. boosting strategy. However, the strategy, with rAdV i.m. priming- rSjTPI s.c. boosting, generated the most optimal protective efficacy and worm or egg reduction rate reaching up to 70% in a mouse model.ConclusionsA suitable immunization strategy, rAdV i.m. priming-rSjTPI boosting strategy, was developed, which elicits a high level of protective efficacy against Schistosoma japonicum infection in mice.
Highlights
In China, schistosomiasis japonica is a predominant zoonotic disease, and animal reservoir hosts in the environment largely sustain infections
Specific immune responses and protective efficacy induced through DNA i.m. priming-Recombinant adenoviral vectored vaccine (rAdV) i.m. boosting strategy against S. japonicum infection Compared to the control or vector immunized group, DNA i.m., rAdV i.m., and DNA i.m. + rAdV i.m. immunization induced significantly higher IgG (ANOVA, F(5,42) = 135.76, P < 0.001), IgG1 (ANOVA, F(5,42) = 33.99, P < 0.001), and IgG2a (ANOVA, F(5,42) = 157.70, P < 0.001) levels and IgG titers (ANOVA, F(5,42) = 78.33, P < 0.001), respectively
Levels of IgG and IgG titers induced by DNA i.m. + rAdV i.m. immunization were significantly higher compared to that induced by DNA i.m. immunization (t-test, t(15) = 15.93, P < 0.001 and, t(15) = 3.24, P = 0.005), but significantly lower compared to that induced by rAdV i.m. immunization (t-test, t(15) = 5.52, P = 0.02 and t(15) = 3.98, P = 0.001) (Fig. 1a, b). rAdV i.m. and DNA i.m. + rAdV i.m. immunization elicited higher IgG avidity when compared to that induced by DNA i.m. immunization, and IgG avidity indices were 0.909, 0.823, and 0.597, respectively (t-test, t(15) = 5.89, P < 0.001 and t(15) = 8.21, P < 0.001) (Fig. 1c)
Summary
In China, schistosomiasis japonica is a predominant zoonotic disease, and animal reservoir hosts in the environment largely sustain infections. The development of transmission-blocking veterinary vaccines is urgently needed for the prevention and efficient control of schistosomiasis. Schistosomiasis transmission has been reported in 78 countries or regions in Africa, Asia and Southern America, and it has been estimated that at least 258.9 million people required preventive treatment in 2014 [3]. In China, schistosomiasis (caused by S. japonicum) is the most severe disease in history. In China, schistosomiasis japonica is a predominant zoonotic disease, and there are more than 40 animal reservoir hosts in the environment, including water buffalo, cattle, pigs and goats, which in turn largely contribute to sustaining the infection [11, 12].
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