Current status of an oral B subunit whole cell cholera vaccine.

Purified B subunit of cholera toxin retains membrane-binding capacity and protective immunogenicity and yet has no toxic activity as tested in animals. These properties suggest that B subunit might be a promising immunogen, particularly as an oral vaccine, for stimulating protective antitoxic immunity against cholera in man. A method has been elaborated which allows preparation of +/- 10 grams of pure B subunit per fermentor culture cycle. As tested in both Swedish and Bangladeshi volunteers purified B subunit alone or in combination with conventional whole cell vaccine gives no side-effects at all when given orally and only very mild local reactions after parenteral administration. A single peroral or intramuscular immunization with B subunit has given significant intestinal IgA antitoxin antibody formation in 75-85% of Bangladeshi women tested; however, the duration of the response was longer after the oral route. The preliminary results of a recent study (Svennerholm, A.M., Jertborn, M., Gothefors, L., Karim, A., Sack, D. and Holmgren, J., to be published) have further shown that two peroral immunizations of Bangladeshi volunteers with a combined B subunit--whole cell cholera vaccine give rise to mucosal IgA antitoxin as well as anti-lipopolysaccharide antibody formation which closely resemble these antibody responses in cholera convalescents. The combined vaccine also evoked a local immunologic memory comparable to that induced by clinical disease.