Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for sa fety reasons. To strengthen its status as a paradigm for a human recombinan t antigen vaccine, we have undertaken a small-scale vaccination and challen ge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, an d parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic st ages of challenge infection up to chemotherapeutic cure. Vaccination induce d a strong in vitro proliferative response and early gamma interferon produ ction, but type 2 cytokines were dominant by the time of challenge. The con trols showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reache d high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccina tion were manifested as an amelioration of acute disease and overall morbid ity, revealed by differences in gamma-glutamyl transferase level, leukocyto sis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 4 6% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection.