Vaccine research and development for the prevention of filarial nematode infections.

Abstract

The development of vaccines for the prevention of filarial nematode infections is in a state of relative infancy in comparison to vaccines for other parasitic diseases, such as schistosomiasis and malaria. There are many reasons for this slow start. Some of the principal problems are: (1) the lengthy and complex life cycle of these organisms with attendant complex immune responses, (2) the unique characteristics associated with a relatively large number of different pathogens, (3) the lack of suitable model systems for study of medically important infections, (4) the paucity of parasite material for antigen discovery and recombinant library construction, (5) the lack of substantial evidence suggesting the natural occurrence of protective immune responses, and (6) the limited data on mechanisms responsible for protective immunity. As technical hurdles are considered, it is also critical to focus on the characteristics of a vaccine necessary for its eventual utility. In the case of a vaccine for D. immitis a completely successful product will need to approach a 99+% efficacy. This is because of the 99+% efficacy of competitive chemotherapeutic products and the fact that microfilaremia observed on blood examination, resulting from as few as two worms, would present as a vaccine failure. Although very low worm burdens in large dogs could be perceived as success in the context of protection from clinical disease, because of the option of virtually complete chemoprophylactic protection, the typical veterinary practitioner would probably fail to appreciate less than complete vaccine protection. In contrast, a vaccine that produced a reduction in adult worm burdens without complete protection in either lymphatic filariasis or onchocerciasis would be very important. Highly effective chemoprophylactic agents are not widely available for prevention of the human filariases, and dramatically reduced clinical disease provided by less than a completely effective vaccine could occur as the result of fewer adult worms. The importance of developing these vaccines has outweighed the obstacles to this research. There has been a great deal of epidemiological and experimental evidence to suggest a vaccine is feasible and antigen discovery has progressed relatively rapidly within just the past few years. Efforts to generate appropriate larval cDNA libraries are beginning to yield dividends and a variety of fascinating vaccine candidates have been cloned. Additional antigen discovery, research on appropriate modalities for overexpression of genes from these parasites, and the complex tasks associated with vaccinology remain as significant research and development obstacles.(ABSTRACT TRUNCATED AT 400 WORDS)