ENTERAL IMMUNIZATION AND CHALLENGE OF VOLUNTEERS GIVEN ENTEROTOXIGENIC ESCHERICHIA-COLI CFA II ENCAPSULATED IN BIODEGRADABLE MICROSPHERES/

The development of a safe and effective vaccine against enterotoxigeni c Escherichia coli (ETEC) would be useful for travellers and for young children in endemic areas. A feasibility study of an enteral ETEC vac cine prototype consisting of colonization factor antigen II (CFA/II), containing two component antigens CS1 and CS3, encapsulated in biodegr adable polymer microspheres (BPM) was conducted in healthy volunteers. Ten adult volunteers swallowed intestinal tubes on days 0, 7, 14 and 28; after collection of jejunal fluid samples, 1 mg of CFA/II in BPM w as administered via the tube. Volunteers kept a diary of symptoms afte r each close. Secretory IgA in jejunal fluids, serum responses and cir culating antibody-secreting cells (ASC) were measured before and after vaccination, The vaccine was well tolerated. Five of ten volunteers d eveloped TgA anti-CFA/II ASC by 7 days after the last dose of vaccine; these same five vaccinees had IgA anti-CS3 ASC, and three of these fi ve vaccinees had IgA anti-CSI ASC. Five of ten vaccinees developed ris es in jejunal fluid sIgA anti-CFA/II with peak GMT of 1:42. About 8 we eks after the first dose of vaccine, ten vaccinees and ten unvaccinate d control volunteers underwent challenge with 10(9) c.f.u. ETEC E24377 A (0139:H28 LT(+) ST+ CS1(+) CS3 +). Ten of ten controls and seven of ten vaccinees developed diarrhoea (p = 0.11, 30% vaccine efficacy). Tw o of the three protected vaccinees had the highest numbers of ASC and highest sIgA titres during the course of immunization, suggesting that these responses were protective and that this vaccine development str ategy has merit. Future studies with higher dosages and a different do sing schedule are planned.