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

Abstract

A single dose (5 x 108 organisms) of attenuated A-B' Vibrio cholerae classical Inaba recombinant vaccine strain CVD 103-HgR or placebo was administered to 24 healthy young Thai adults in a randomized, placebo-controlled, double-blind trial of safety and immunogenicity. None of the volunteers experienced untoward reactions. The vaccine strain was recovered from 2 of 12 vaccinees. The vibriocidal antibody response (the best immunological correlate of protection) was good: 11 of 12 vaccinees (92%) manifested significant serotype-homologous Inaba antibody rises with a peak reciprocal geometric mean titer (RGMT) postvaccination of 3,417; 9 of 12 exhibited significant serotype-heterologous Ogawa antibody rises (prevaccination RGMT, 180; peak RGMT, 2,874). Nine of 12 vaccinees had significant rises in serum antitoxin. None of the controls exhibited rises in vibriocidal or antitoxic antibody. This preliminary study further confirms the safety and immunogenicity of CVD 103-HgR live oral cholera vaccine and paves the way for larger community zation with a combined B subunit/whole cell vaccine. J. Infect.

Phase 1 Evaluation ofVibrio choleraeO1, Serotype Inaba, Polysaccharide-Cholera Toxin Conjugates in Adult Volunteers

“…Parenterally administered cellular cholera vaccines, as with other gram-negative bacteria (8,13,22,33), elicit high levels of mainly IgM anti-LPS for about 6 months. The rapid decline of this IgM vibriocidal activity explains the short-lived protection conferred by cellular vaccines (5,16,24,25,31).…”

“…Absorption of vibriocidal activity was assayed by mixing equal volumes of 200 g of LPS, DeALPS, or CT per ml with equal volumes of dilutions of antisera at 37°C for 1 h prior to addition of the bacteria (11,26). Inactivation of IgM was done by mixing equal volumes of sera and 0.2 M 2-mercaptoethanol (2-ME) and incubating at 4°C overnight (22). The sera were dialyzed against phosphate-buffered saline at 4°C with three changes of the outer fluid, and the vibriocidal activity was assayed (22).…”

“…Inactivation of IgM was done by mixing equal volumes of sera and 0.2 M 2-mercaptoethanol (2-ME) and incubating at 4°C overnight (22). The sera were dialyzed against phosphate-buffered saline at 4°C with three changes of the outer fluid, and the vibriocidal activity was assayed (22).…”

Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels

“…Genetically engineered attenuated Vibrio cholerae 01 strain CVD 103-HgR (6, 9, 10) has shown considerable promise as a single-dose live oral vaccine in phase 1 and 2 studies in adult and pediatric populations in cholera-endemic areas (8,14,18,19) and in adults from industrialized countries (3,4,7,9,10). For the latter group, a single dose of CVD 103-HgR has conferred significant protection against experimental cholera, with protection commencing as early as 8 days and continuing for at least 6 months after vaccination (21).…”

Safety and immunogenicity in North Americans of a single dose of live oral cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double-blind crossover trial

“…CVD 103-HgR is a live oral cholera vaccine strain constructed by recombinant DNA methods from classical Inaba strain 569B by deletion of the genes encoding the A subunit of cholera toxin and introduction of a gene encoding resistance to Hg+ (as a marker) into the hlyA locus of the bacterial chromosome (5,6,9). Heretofore, this vaccine has been extensively tested in randomized, placebo-controlled trials in adults and children in less-developed countries, where it has been well tolerated and has elicited high rates of seroconversion of vibriocidal antibody (11,13,15,16). The goal in such populations is to evaluate CVD 103-HgR as a possible tool in the control of endemic and epidemic cholera.…”