Evaluating Vaccine Candidates for Filariasis
Uniformed Services University Of The Health Sciences Bethesda United States
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Parasites of the family Onchocercidae, commonly referred to as filarial worms, can cause severely devastating conditions such as elephantiasis and blindness. While there are programs currently in place to try to control or eradicate these diseases through mass drug administration, there are no vaccines available to prevent infection with these pathogens. There has been an interest in vaccination with hidden antigens, antigens to which the host does not mount an adaptive immune response during infection, in helminths. We found that the soluble fraction of the intestine GutAg of L. sigmodontis exhibits some hidden qualities, in that IgG antibody titers to these antigens are much lower than to the soluble fraction of the whole worm LsAg, and that cytokine production by splenocytes is lower in response to GutAg than to LsAg. However, immune responses associated with allergy, including IgE titers and Basophil activation, were similar in response to LsAg and GutAg. Furthermore, vaccination with GutAg and CpGAlum was not protective against challenge infection. Similarly, a vaccination protocol using LsAg and CpGalum did not protect against challenge infection. However, vaccination with irradiated larvae results in around 80 protection, yet this method of vaccination is not practical in humans. We hypothesized that comparing the immune responses in the irradiated larval vaccinated mice compared to the LsAg vaccinated mice may provide some insight into future methods of vaccination. We found that while vaccination with irradiated larvae iL3 and LsAg with CpGAlum induced similar IFN- production in response to LsAg, IL-4 production was much higher in the iL3 vaccinated mice. Vaccination with LsAg adsorbed to alum induced strong IL-4 responses to LsAg, but again did not result in a protective immune response.