INDUCTION OF SPECIFIC CELL-MEDIATED-IMMUNITY IN MICE BY ORAL IMMUNIZATION WITH SALMONELLA EXPRESSING ONCHOCERCA-VOLVULUS GLUTATHIONE-S-TRANSFERASE

Cellular and humoral immune responses of mice to Onchocerca volvulus g lutathione S-transferase (OvGST) presented via in vivo expression in a ttenuated Salmonella typhimurium were examined and compared with the s ame antigen administered by subcutaneous injection with Freund's adjuv ant. After infection with recombinant S. typhimurium, maximal numbers of bacteria were recovered from the mesenteric lymph nodes and spleens during the second week postinfection. By weeks 3-4, bacteria were abs ent from these tissues. Splenocytes from mice infected with S. typhimu rium expressing OvGST showed significant and specific proliferative re sponses to OvGST, whereas the non-recombinant S. typhimurium controls and those which received the antigen by subcutaneous injection with Fr eund's adjuvant did not. Mice infected with recombinant S. typhimurium had elevated IFN-gamma levels over non-recombinant S. typhimurium and placebo controls, but IL-4 and IL-5 levels were low and did not diffe r significantly between these groups. Antibody responses to OvGST anti gen expressed by a recombinant Salmonella vaccine or delivered in a pu rified form with Freund's adjuvant were moderate to high. These data s uggest that Salmonella can be used as a vaccine delivery vector that i nduces specific cellular and humoral immune responses to Onchocerca vo lvulus antigens. This is the first report to describe the successful a pplication of a filarial antigen in a live-vector delivery system as w ell as the first recombinant based filarial vaccine to elicit a cellul ar immune response similar to that described for putative immune endem ics. (C) 1998 Elsevier Science Ltd. All rights reserved.