Content of review 1, reviewed on January 21, 2014

Significance Comment

See above

Quality Comment

Schistosoma mansoni Sm-p80 vaccine confers protection against Schistosoma haematobium in hamsters and baboons”. This abstract caught my attention for a number of reasons. First, although I am not currently engaged in schistosome vaccine research, I would love to be so. Second, I am keenly interested in the potential applications and limitations of various animal models of urogenital schistosomiasis. Despite hamsters being suitable hosts for S. haematobium infection, they tend to develop hepatoenteric schistosomiasis, rather than urogenital disease like S. haematobium-infected humans. This greatly limits the value of hamsters for urogenital schistosomiasis research.

Indeed, the authors of this Vaccine article noted no urogenital pathology in any of their 7 vehicle- and 10 vaccine-treated hamsters, all of which had been infected with S. haematobium. Remarkably, this was true even after 28 weeks of infection. As the authors stated, “in this study no eggs were detected in the urinary bladder of hamsters either in the control or the experimental group. This drawback limits the suitability of hamsters as a model to study S. haematobium-associated pathogenesis to the fullest.” The authors then go on to note that “the lack of an experimentally tractable small animal model has significantly limited our knowledge of vaccine efficacy and mechanistic aspects related to the urogenital schistosomiasis pathogen, S. haematobium”. This statement, which echoes my sentiments exactly, is followed by a citation of our 2012 PLOS Pathogens paper describing the first tractable animal (mouse) model of S. haematobium egg-induced bladder pathology. Like hamsters, mice that are naturally infected through the skin with S. haematobium cercariae, the larval stage infective for humans, develop hepatoenteric rather than urogenital disease. In our PLOS Pathogens paper we bypassed this problematic life cycle by directly microinjecting S. haematobium eggs into the mouse bladder wall, thereby delivering the parasite life stage of interest into the host tissues of interest.

The authors of the Vaccine paper remarked that “even though statistically significant data were obtained from the hamster model on prophylactic efficacy, the absence of eggs in the urinary bladder indicated a better model was needed and led us to develop and optimize a S. haematobium model in baboons”. I applaud the authors for their determination to develop and test their vaccine in a higher fidelity experimental model of urogenital schistosomiasis. It has long been known that baboons are suitable hosts for S. haematobium infection, but non-human primate studies, including those using baboons, suffer from a lack of species-specific reagents, logistical difficulties (due to costs and housing needs), and are ethically contentious. Accordingly, the authors were only able to test a total of four baboons – 2 receiving vehicle injections, and 2 receiving the candidate vaccine. Fortunately the authors were able to obtain favorable data on egg counts in the bladder and urine of these baboons, but their findings are statistically limited by the small sample size.

One of the authors’ interesting findings is that the candidate vaccine seemed to induce gamma-interferon and IL-17-secreting peripheral blood mononuclear cells. This suggests that the vaccine induced antigen-specific cytokine secretion. Overall I was thrilled by this paper and I hope the vaccine succeeds.

Source

    © 2014 the Reviewer (CC BY-SA 3.0).

Comments   (Guidelines)

4:18 a.m., 3 Apr 14 (UTC) | Link

First of all, I want to thank you for appreciating our effort towards the development of anti-schistosoma vaccine and putting comments on that. The reduction in worm and egg production in vaccinated hamster group motivated us to perform a preliminary study with less number of baboons because of the costs constrains. Since now we have some convincing results in baboons with regards to the reduction in egg deposition in the urinary bladder, it would not be difficult to carry on vaccine studies for S. haematobium infection or urinary bladder schistosomiasis in far future with more baboons.

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