Immunogenicity of two formulations of oral cholera vaccine comprised of killed whole vibrios and the B subunit of cholera toxin

Abstract

Two formulations of oral cholera vaccine were evaluated for safety and immunogenicity in adult volunteers in Thailand, an area with sporadic cholera outbreaks. One formulation consisted of 2 x 1011 killed vibrios and 5 mg of cholera toxin B subunit, as was previously evaluated in North American volunteers, and the other consisted of 1 x 1011 killed vibrios and 1 mg of B subunit, as was recently evaluated in a field trial in Bangladesh. Three doses of each formulation were given with citrate-bicarbonate buffer. Neither formulation had adverse effects. The formulations stimulated similar serum immunoglobulin G (IgG) and IgA responses to Vibrio cholerae lipopolysaccharide and cholera toxin and intestinal secretory IgA responses to lipopolysaccharide and toxin after three doses. The formulation containing twice the quantity of killed vibrios stimulated better vibriocidal responses, especially to Ogawa serotype. A formulation of oral vaccine containing more killed vibrios than were included in the vaccine studied in the Bangladesh field trial may provide greater protection against cholera. Cholera provides considerable immunity against subsequent illness due to Vibrio cholerae for several years (7). However, parenteral vaccination with killed vibrio preparations offers only partial protection for less than 6 months (9, 13). With the recognition of the importance of local intestinal immunity against V. cholerae, attention has turned to the development of oral vaccines (9). In addition, with the understanding that cholera stimulates the production of both antibacterial and antitoxic antibodies in the intestine, emphasis has been given to combining elements in an oral vaccine to provoke an immune response against cholera toxin as well as against the organism itself (14, 15).Vaccines consisting of killed whole V. cholerae organisms and the purified B subunit of cholera toxin have been extensively evaluated. A single dose consisting of 2.5 mg of the B subunit and 5 x 1010 killed vibrios stimulated a local secretory immunoglobulin A (sIgA) antitoxin response and, in most, a sIgA antilipopolysaccharide (anti-LPS) response comparable to responses induced by cholera (15). Three doses, each comprising 5 mg of B subunit and 2 x 1011 killed vibrios or the killed vibrios alone, were studied for protective efficacy in North American adult volunteers (2). The combination oral vaccine provided 64% protection against cholera and the oral killed V. cholerae vaccine gave 56% protection. In a field trial subsequently performed in Bangladesh, an area where cholera is endemic, three doses of 1 mg of B subunit and 1011 killed whole vibrios were found to provide 62% efficacy, while the killed-vibrio vaccine alone gave 53% protection in the year after vaccination (3, 5). Since the formulation evaluated in volunteers and that tested in the field were never compared for immunogenicity, we chose to do so in adults in Thailand, an area with sporadic cholera outbreaks (recently due primarily to V. cholerae El Tor Inaba serotype). * Corresponding a...

The ABCs (Antibody, B Cells, and Carbohydrate Epitopes) of Cholera Immunity: Considerations for an Improved Vaccine

“…Because cholera is an enteric disease it has long been surmised that V. cholerae-specific sIgA, which is secreted into the gut lumen, provides the protective response and thus should be the goal of immunization (102). Indeed, increased levels of sIgA specific against V. cholerae LPS have been found in convalescent sera and intestinal secretions of patients recovering from cholera (139,160,190). Those individuals living in endemic cholera areas have anamnestic sIgA response to V. cholerae vaccination (223,224).…”

“…The most extensively studied new generation vaccine is a killed WC cholera vaccine, containing either heat-or formalin-killed bacteria of the classical and El Tor biotypes admixed with CT subunit B (CTB) (46,225). Killed V. cholerae vaccines have been tested in volunteers and in field trials (46,160). Field-testing of WC-CTB vaccines revealed excellent protective efficacy (85%) in the first 12 months which was reduced to ϳ50% over 3 years (46).…”

“…Vaccination has been shown to be very effective in Western volunteers challenged under laboratory conditions (145). In a large clinical trial of CVD 103-HgR, different levels of efficacy were reported among vaccinees from disparate parts of the world (86,160,210). The overall protective effect of the vaccine was low (18%), but evaluation was complicated by the cholera case rate (195).…”

Properties of practical oral liposome‐Streptococcus mutans glucosyltransferase vaccines for effective induction of caries protection

“…Most infectious organisms invade or colonize mucosal tissues; therefore an important strategy for the prevention of many diseases is to establich means for inducing S-IgA immune responses. Studies in humans and animals (21,(23)(24)(25)29) have demonstrated that oral administration of microbial antigen vaccines result in the presence of antigenspecific IgA antibodies in several different glandular secretions via the common mucosal immune system (24).…”

Preliminary assessment of the safety and immunogenicity of live oral cholera vaccine strain CVD 103-HgR in healthy Thai adults

“…The volunteers were from middle-class and lower-middle-class backgrounds and included university students and graduates of a vocational school. To ensure the informed nature of the consent process, the volunteers had to pass a written examination consisting of approximately 20 true-or-false questions on all aspects of the study (8,14). The 24 volunteers were randomized to receive a preparation coded A, B, C, or D, two of which were vaccine and the other two placebo.…”