Kunitz-type protease inhibitor as a vaccine candidate against schistosomiasis mansoni

• Published in: International journal of infectious diseases Vol. 66; no. C; pp. 26 - 32
• Main Authors: Ranasinghe, Shiwanthi L., Duke, Mary, Harvie, Marina, McManus, Donald P.
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01.01.2018; Elsevier
• Subjects: Animals; Antigens, Helminth - immunology; Egg Hypersensitivity; ES products; Female; Interferon-gamma; Interleukin-10; Interleukin-6; Kunitz protein; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Protease Inhibitors - immunology; Schistosoma mansoni; Schistosomiasis mansoni; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - prevention & control; SmKI-1; Vaccines - immunology; Schistosomiasis mansoni; SmKI-1; Kunitz protein; ES products
• ISSN: 1201-9712; 1878-3511; 1878-3511
• DOI: 10.1016/j.ijid.2017.10.024

[Display omitted] •The vaccination of mice with rSmKI-1 resulted in reduced numbers of parasites and eggs.•The rSmKI-1 vaccine produced a solid IgG response, with the IgG1 isotype being predominant.•The rSmKI-1 vaccine down-regulated the Th2 immune response, reducing disease pathology.•SmKI-1 has potential for development as part of a schistosomiasis cocktail vaccine. The aim of this study was to develop a vaccine against schistosomiasis, which is a major challenge due to the complex lifecycle of the causative schistosome parasite. SmKI-1 is a 16-kDa Kunitz-type protease inhibitor present in the excretory–secretory products and tegument of adult worms and eggs of Schistosoma mansoni. Two independent vaccine trials were performed in mice to determine the efficacy of rSmKI-1 in developing protective immunity. The results obtained showed reductions of 23–33% in adult worms, 28–31% in intestinal eggs, 33–39% in faecal eggs, and 20–43% in liver eggs. Furthermore, rSmKI-1 significantly increased the production of interferon gamma, interleukin (IL)-10, and IL-6 in vaccinated mice, maintaining a Th1/Th2-type balanced protective response. rSmKI-1 generated partial protection against schistosomiasis mansoni in the murine model of infection and could be developed as part of a combination vaccine with other vaccine candidates to provide an even more solid level of protection.