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Schistosome Vaccine- Vaccine Development


Vaccine Development

Considerations of vaccine development are assessed within the context of the host immune response against schistosome infection. The Th1-Th2 immune modulation has been the subject of intense investigation because of their potential for vaccine. One of the recent studies by Jankovic et al. has showed by using knockout mice for interferon-gamma and B-cell depletion that both cell-mediated and humoral immunity are essential for further vaccine development against schistosomiasis. Instead of complete protection, schistosomiasis vaccine research has rather focused on the optimization of at least partial immunity. This theory has been advanced for a number of reasons. First is it hard to achieve sterilizing immunity and secondly most candidate antigens studied up until now fails to produce anything significant beyond the 50-60% mark. But this level of efficacy while promising has not yet been demonstrated in humans. Most of what we know so far comes from animal models. For instance, as reported by Liben et al., some murine studies have showed up to 80% sterilizing immunity when irradiated cercariae, or radiation-attenuated vaccine (RA) vaccine is used. However, addition of IL-12 has also been shown to increase the efficacy of such vaccines by acting as adjuvants.  Furthermore, McManus et al. also reports on development in areas of antibody-dependent cell mediated cytotoxicity (ADCC) as other possible mechanism of vaccine exploration against schistosomes. ADDC uses IgE, IgG, and IgA in conjunction with other effector cells including macrophages, eosinophils, and platelets and this experiment has been done in both primates and humans. In some isolated cases it has also been reported that older individuals tend to acquire immunity which shows a tendency for Th2 to play a more important role than that of Th1. The main problem remains that there is still much to be unraveled about the exact role for cytokines in mediating the parasite-host immune interaction. However, many studies make it clear that both cytokines of Th1 and Th2 are actively involved in the host’s immune response. Of a particular interest in schistosomiasis vaccine development is that of acquired immunity. Many immunological researches have shown that some people become resistant to re-infection while others are still susceptible to infection. Higher expression of IgE has been shown to confer protection in some individuals. However, IgG-4 also does the opposite. Hence, studies with S. mansonic and S. hematobium infection has showed that IgE is protective while IgG make the individual more susceptible for infection.  In addition, the acquired immunity is also involved. Genetic polymorphism is also one of the areas implicated in the quest for vaccine research in schistosomiasis. For instance studies from Brazil with S.mansoni IgG antibodies against a 37-kDa molecule, glyceraldeydge-3-phosphate dehydrogenase (GAPDH) resulted in resistance to re-infection. Also IgA against a glutathione S-transferase, which is a 28-kDa antigen derived from schistosome showed resistance against infection with S.mansoni in Kenya.