Longevity of Sm-p80-specific antibody responses following vaccination with Sm-p80 vaccine in mice and baboons and transplacental transfer of Sm-p80-specific antibodies in a baboon

Abstract

Based on data obtained using vaccine efficacy studies in mice, hamsters, and baboons, the credentials of Sm-p80 as a first tier vaccine candidate for schistosomiasis have been well established. Sm-p80-based vaccine formulation(s) have consistently exhibited potent prophylactic efficacy in reducing adult worm burden following cercarial challenge and induce killing of established adult worms in chronic infection. This vaccine is protective against both intestinal and urinary schistosomiasis. In this study, the longevity of Sm-p80-specific antibody responses was studied in mice and in baboons. Robust antibody titers were detected in mice for up to 60 weeks following vaccination with Sm-p80 recombinant vaccine (Sm-p80 + GLA-SE). In the follow-up experiments to our published studies, Sm-p80-specific IgG was also detected in baboons 5-8 years following the initial vaccination with an Sm-p80 DNA vaccine. In one baboon, transfer of Sm-p80-specific antibody was detected in umbilical cord blood and in the baby. These long-lasting humoral immune response data coupled with the vaccine efficacy data in rodents and nonhuman primates further strengthens the case for Sm-p80 to be moved forward through development leading to human clinical trials.

Sm-p80-Based Schistosomiasis Vaccine: Preparation for Human Clinical Trials

“…Sm-p80 is present in the surface membranes and syncytium of the worm; is the highly immunodominant antigen in the membranes; and exhibits no immunological cross-reactivity with human and other vertebrate calpains [42]. Briefly, Sm-p80 has been tested for its vaccine efficacy in different vaccine formulations and approaches including naked DNA, recombinant protein and prime/boost in three experimental animal models of infection and disease (mouse, hamster and baboon) [43-49]. Sm-p80-based vaccine formulation(s) have many effects: (i) prophylactic efficacy against intestinal/hepatic schistosomiasis; (ii) egg induced pathology resolution both in rodents and baboons; (iii) post-exposure therapeutic effect via killing of established adult worms in chronic infections; (iv) cross-protection against urinary and Asiatic/oriental schistosomiasis; (v) longevity of immune response–robust antibody titers in mice for up to 60 weeks and 5-8 years in baboons; (vi) transplacental transfer of Sm-p80-specific antibodies in baboons.…”

“…Sm-p80-based vaccine formulation(s) have many effects: (i) prophylactic efficacy against intestinal/hepatic schistosomiasis; (ii) egg induced pathology resolution both in rodents and baboons; (iii) post-exposure therapeutic effect via killing of established adult worms in chronic infections; (iv) cross-protection against urinary and Asiatic/oriental schistosomiasis; (v) longevity of immune response–robust antibody titers in mice for up to 60 weeks and 5-8 years in baboons; (vi) transplacental transfer of Sm-p80-specific antibodies in baboons. As depicted in Figure 2, the Sm-p80-based vaccine has multifaceted effectiveness against several stages of the parasite’s life cycle, including eggs, schistosomula and adult worms [43-49]. Additionally, Sm-p80-specific IgE has not been detected in high risk or infected populations from Africa [45] and South America [50], thus minimizing the risk of hypersensitivity reaction following vaccination with Sm-p80-based vaccine in humans.…”

Development of a schistosomiasis vaccine

“…Over the last two decades, our group has followed a systematic and methodical approach to develop Sm-p80 as a viable and effective schistosomiasis vaccine. To our knowledge, Sm-p80 is the only schistosome vaccine candidate that has been tested for its prophylactic, anti-fecundity and therapeutic efficacy in different vaccine formulations and immunization approaches (DNA vaccine alone; recombinant protein with adjuvants; and priming with DNA vaccine, followed by boosting with protein plus adjuvants) in three experimental animal models (mice, hamsters and baboons) of infection and disease [44–53]. Sm-p80 vaccine formulations in both mice and baboons induced high levels of protection and anti-fecundity effects approaching those that could only be previously achieved with the attenuated cercarial vaccine approach [44;48].…”

Developing a mathematical model for the evaluation of the potential impact of a partially efficacious vaccine on the transmission dynamics of Schistosoma mansoni in human communities

“…However, experiments in mice, rodents, hamsters and baboons infected with S. mansoni , have shown partial prophylactic and anti-fecundity efficacies using various candidate formulations, including recombinant Sm-p80 protein and DNA priming followed by boosting with various parasite proteins [6, 11–15]. Recombinant protein with the Sm-p80 antigen is the leading vaccine candidate at present [16, 17].…”

“…In this paper, based on recent pre-clinical studies in primates [6, 14, 15], we describe the development of a simple deterministic mathematical model which details the dynamics of the human host and adult parasite populations, to assess the impact of a potential vaccination programme that is applied to a community. The model has a general framework such that it can mirror different vaccine delivery strategies, namely infant and mass immunisation.…”