Cross-species protection: Schistosoma mansoni Sm-p80 vaccine confers protection against Schistosoma haematobium in hamsters and baboons

Abstract

The ability of the Schistosoma mansoni antigen, Sm-p80, to provide cross-species protection against Schistosoma haematobium challenge was evaluated in hamster and baboon models. Pronounced reduction in worm burden (48%) and in tissue load (64%) was observed in hamsters vaccinated with recombinant Sm-p80 admixed with Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE). Similarly, in baboons, the Sm-p80 / GLA-SE vaccine produced a 25% reduction in S. haematobium adult worms and decreased the egg load in the urinary bladder by 64%. A 40% and 53% reduction in fecal and urine egg output, respectively, was observed in vaccinated baboons. A balanced pro-inflammatory (Th17 and Th1) and Th2 type of response was generated after vaccination and appears indicative of augmented prophylactic efficacy. These data on cross-species protection coupled with the prophylactic, therapeutic and antifecundity efficacy against the homologous parasite, S. mansoni, reinforces Sm-p80 as a promising vaccine candidate. It is currently being prepared for GMP-compliant manufacture and for further pre-clinical development leading to human clinical trials. These results solidify the expectation that the Sm-p80 vaccine will provide relief for both the intestinal and the urinary schistosomiasis and thus will be greatly beneficial in reducing the overall burden of schistosomiasis.

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).…”

“…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). Based on the findings from our recent study which evaluated the cross-species protective efficacy of Sm-p80-based vaccine against urinary schistosomiasis in hamsters and baboons in which Sm-p80 vaccine offered significant protection against S. haematobium infections (Karmakar et al 2014a), we hypothesized that protection against Asiatic schistosomiasis caused by S. japonicum infections would be possible by inducing specific host immune responses through Sm-p80-based vaccination. The data presented here from the two independent S. japonicum vaccine trials showed that Sm-p80 vaccine conferred significant cross-species protection against Asiatic schistosomiasis in mice.…”

“…Several studies by our group have shown that Sm-p80 vaccine is highly efficacious against S. mansoni infections in mice and baboons (Ahmad et al 2009a; Ahmad et al 2009b; Ahmad et al 2009c; Karmakar et al 2014b; Le et al 2014). Of equal importance is the finding from our recent study which showed that Sm-p80 vaccine formulated in Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) conferred cross-species prophylactic protection against S. haematobium infections in both hamster and baboon models (Karmakar et al 2014a). GLA-SE is a Toll-Like Receptor 4 (TLR4) agonist and a potent stimulator of antigen presenting cells currently being used in many commercially available vaccine formulations (Coler et al 2011; Garcon and Van Mechelen 2011).…”

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

“…GLA adjuvant formulations have been used with experimental vaccines for influenza, HIV (29), respiratory syncytial virus (RSV) (30), leishmaniasis (31), malaria (32), and leprosy (33) in addition to TB (34,35). Many of these vaccines using GLA formulations have also resulted in protection in preclinical animal models, including mice (34)(35)(36), ferrets (37,38), guinea pigs (34,35,39), cotton rats (30), and hamsters (40), against infectious challenge.…”

Still hope for schistosomiasis vaccine

“…These levels of protection have previously never been seen with a schistosome antigen in large animal models. Furthermore, in addition to prophylactic efficiency, the Sm-p80 immunizations could also induce killing of established adult worms and protect against urinary schistosomiasis caused by S. haematobium28 .…”