Schistosoma mansoni antigen Sm-p80: Prophylactic efficacy of a vaccine formulated in human approved plasmid vector and adjuvant (VR 1020 and alum)

Abstract

Schistosomiasis is an important parasitic disease. Consensus is developing now that ideal control methods of the disease should be based on an integrated approach incorporating drug treatment, sanitation improvement, education, and an effective vaccine. With regards to the vaccine development, Sm-p80 has been shown to be a promising and strong immunogenic vaccine candidate. In the present study, Sm-p80-based vaccine formulated in alum was tested for its prophylactic efficacy in a mouse model. It was observed that vaccination using heterologous prime boost (DNA prime followed by boost with protein formulated in alum) and homologous prime boost (both prime and boost with protein formulated in alum) approaches, resulted in 61% and 55% reduction in worm burden, respectively. The protection was directly correlated with the induction of high titers of antibody responses that mainly included IgG, its isotypes, and IgM. In addition, both of the immunization approaches triggered a mixed Th1 and Th2 type response. Some involvement of Th17 specific immune response was also detected as indicated by the upregulation of relevant cytokines. These results reinforce the potential of Sm-p80 as a viable vaccine candidate.

Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium

“…Over the last two decade, we have employed a systematic approach to developing Sm-p80-based vaccine for schistosomiasis control. Several studies by our group using various Sm-p80-based vaccination strategies have demonstrated high levels of prophylactic and therapeutic efficacy against S. mansoni infections in both mice and baboons (Ahmad et al 2009a; Ahmad et al 2009b; Ahmad et al 2009c; Karmakar et al 2014a; Karmakar et al 2014b; Le et al 2014; Zhang et al 2010b; Zhang et al 2011); efficacy levels obtained with Sm-p80 vaccine are comparable to previously obtained data with S. mansoni radiation attenuated (RA) cercariae vaccine, which is a gold standard for anti-schistosome protective immunity. Immunizations with the RA vaccine have been demonstrated to show significant protection levels ranging from 56% to as high as 80% following cercariae challenge (Anderson et al 1999; Ganley-Leal et al 2005; Sher et al 1982; Wilson et al 1999).…”

“…In the RA model, co-administration of IL-12 (a potent Th1 inducing cytokine) with RA vaccine resulted in almost sterile immunity which was associated with a high induction of IFN-γ in an autocrine manner (Wilson and Coulson 2009; Wilson et al 1999; Wilson et al 2016). Studies by our group and other colleagues have shown that the production of IFN-γ is associated with protection against schistosome infection in animal models (Ahmad et al 2009c; Le et al 2014; Pearson et al 2012; Varaldo et al 2004; Zhang et al 2011). The protective role of TNF-α against schistosomiasis has also been demonstrated by the RA vaccine model (Street et al 1999).…”

Immunization with rP22 induces protective immunity against Schistosoma mansoni: Effects on granuloma down-modulation and cytokine production

“…Recently, publications have shown that some proteins located in the tegument, such as TSP-2 [27] and Sm-p80 [37], are able to induce high levels of protection against S. mansoni infection in the murine model. To determine if rP22 conferred protection against S. mansoni infection, immunized mice were challenged with cercariae and worm burdens were assessed.…”

Effect of vaccine administration modality on immunogenicity and efficacy

“…Inactivated whole influenza virus prime followed by split influenza vaccine boost elicited enhanced antibody and protective immune responses when compared with whole virus vaccine alone in mice[26]. DNA vaccine prime/protein vaccine boost induced better antibody and T cell responses then either type of vaccine alone against Schistosomiasis in mice[27], influenza HA DNA vaccine prime followed by trivalent split vaccine boost generated significantly improved protective antibody responses compared to either vaccine alone in rabbits[28], and HIV-1 gp120 DNA vaccine prime-protein boost elicited better neutralizing antibody responses compared to DNA or protein alone HIV in rabbits[29-31]. H5N1 influenza HA DNA vaccine prime-inactivated vaccine boost had significantly improved immunogenicity compared to inactivated vaccine alone in humans[23].…”