THE EFFECTS OF IMMUNIZING OLIVE BABOON, Papio anubis, AGAINST Schistosoma mansoni WITH SNAIL SOLUBLE PROTEINS, AND THEIR IDENTIFICATION

Abstract

Schistosomiasis infects about two hundred million people around the world. Currently, treatment for Schistosoma mansoni infection is by use of Praziquantel. However, a longer lasting solution would be a vaccine to enhance the use of drugs. Unfortunately, no human vaccine againt schistosomiasis is available. Snails that are the intermediate host of S. mansoni have been discovered to have common proteins with the schistosome worms. Research conducted in a mouse model showed that two candidate vaccines derived from Biomphalaria pfeifferri, RT1 (soluble proteins from the rest of snail tissue) and DG1 (soluble proteins from the digestive gland), were protective against S. mansoni. Both candidates met the World Health Organization criteria of over 40% protection. This study was undertaken to evaluate potentials these vaccines in Papio anubis as hosts. The baboons were divided in four groups, 3 groups comprising of three baboons: Two experimental groups, DG (Baboons immunized with DG and then challenged with S. mansoni), RT (Baboons immunized with RT and then challenged with S. mansoni), one control IC (Baboons only infected with S. mansoni) and the Naïve group comprising of 2 baboons. The study involved vaccination of baboons followed by challenge with S. mansoni cercariae. At the beginning of the experiment (minus week 9), DG and RT groups were vaccinated each with their specific protein. In minus week 6 and minus week 3, DG and RT groups were boosted with their specific protein. Three weeks after final vaccination (0 wk), baboons in the 3 groups were infected with 600 cercariae of S. mansoni. At Week six post challenge, perfusion to recover adult worms was carried out on the 3 groups of baboons. Chemical identification and toxicity test of the proteins was done. Results revealed that baboons immunized with snail soluble proteins were better protected than non-vaccinated baboons. The mean worm burden was higher in IC group than both DG and RT group of baboons. Worm reduction in DG was significantly higher (p≤0.05) at 11.44% while in RT it was 6.14%. In cellular responses, DG significantly stimulated increased IL-6 production and consequently resulted in Th2 protection in olive baboons. Percentage CD4, CD8 and CD25 counts in the spleen, lymph node and blood were similar in DG and RT (p>0.05). In humoral responses, both DG and RT stimulated higher production of IgM in a similar manner at most sampling points than the IC, causing agglutination and cytolytic reactions suggesting both DG and RT antigens offered protection to the baboons. Both DG and RT stimulated higher production of IgG in a similar manner at most sampling points than IC, an indication that more worms were killed using antibody dependent cell-mediated cytotoxicity (ADCC). DG had least gross pathology and histopathology indicating that DG baboons were better protected than those from RT and IC. Brine shrimp lethality bioassay results for DG and RT snail soluble proteins at the three different concentrations showed that both proteins were non-toxic and are therefore safe vaccines. Chemical identification of DG and RT using the GC-MS spectrum established the presence of different chemical compounds with varied retention times. The results from the GC-MS were confirmed by UV spectrum and the FTIR results which confirmed the presence of proteins. This was evidenced by the amide (peptide) bands in both cases of the DG and RT soluble protein extracts. In conclusion therefore, although the two vaccine candidates were protective, they fell below the 40% protection threshold of the World Health Organization. Baboons in the DG exhibited greater worm reduction, greater cellular and humoral responses and minimum pathology, therefore making it a better vaccine candidate.