Oral immunization of adult volunteers with microencapsulated enterotoxigenic Escherichia coli (ETEC) CS6 antigen.

As a step in the development of an oral vaccine against ETEC, we evaluated the safety and immunogenicity of CS6, a polymeric protein commonly found on the surface of ETEC. Formulations included 1 and 5mg doses of CS6, either encapsulated in biodegradable polymer poly(D, L)-lactide-co-glycolide (PLG), or as free protein, administered orally in a solution of either normal saline or a rice-based buffer. Three doses of CS6 were given at 2-week intervals. Blood was collected immediately before and 7 days after each dose. All formulations were well tolerated. Four of five volunteers who received 1mg CS6 in PLG microspheres with buffer had significant IgA ASC responses (median=30 ASC per 10(6) PBMC) and significant serum IgG responses (median=3.5-fold increase). Oral administration of these prototype ETEC vaccine formulations are safe and can elicit immune responses. The ASC, serum IgA, and serum IgG responses to CS6 are similar in magnitude to the responses after challenge with wild-type ETEC [Coster et al., unpublished data]. Further studies are underway to determine whether these immune responses are sufficient for protection.