Safety, immunogenicity, and transmissibility of single-dose live oral cholera vaccine strain CVD 103-HgR in 24- to 59-month-old Indonesian children.

Recombinant A-B+ Vibrio cholerae O1 strain CVD 103-HgR is a safe, highly immunogenic, single-dose live oral vaccine in adults in industrialized countries. Safety, excretion, immunogenicity, vaccine transmissibility, and environmental introduction of CVD 103-HgR were investigated among 24- to 59-month-old children in Jakarta. In 81 households, 1 child was randomly allocated a single dose of vaccine (5 x 10(9) cfu) and another, placebo. Additionally, 139 unpaired children were randomly allocated vaccine or placebo. During 9 days of follow-up, diarrhea or vomiting did not occur more often among vaccines than controls. Vaccine was minimally excreted and was isolated from no controls and from 1 (0.6%) of 177 unvaccinated family contacts. A 4-fold or higher rise in serum vibriocidal antibody was observed in 75% of vaccines (10-fold rise in geometric mean titer over baseline). Of 135 paired placebo recipients or household contacts, 5 had vibriocidal seroconversions. Moore swabs placed in sewers and latrines near 97 households failed to detect vaccine. These observations pave the way for a large-scale field trial of efficacy.

Safety and immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR in 5-9-year-old Indonesian children.

Oral vaccines offer great promise as public-health measures to prevent disease in less-developed countries. CVD 103-HgR, a genetically engineered, attenuated, Vibrio cholerae O1 strain has proved effective in industrialised countries. We have assessed the safety, immunogenicity, and excretion of this live cholera vaccine in children in north Jakarta, Indonesia. 412 children aged 5-9 years received single doses of 5 x 10(6), 5 x 10(7), 5 x 10(8), 5 x 10(9), or 1 x 10(10) colony forming units (CFU) of CVD 103-HgR or placebo (5 x 10(8) inactivated Escherichia coli K-12) with buffer. All doses were well tolerated. The 5 x 10(8) CFU dose, which is highly immunogenic in subjects in industrialised countries (greater than 90% seroconversion), elicited seroconversions of vibriocidal antibody in only 16% of Indonesian children. By contrast, a single 5 x 10(9) CFU dose of vaccine resulted in high rates (75% and 87%) of seroconversion with two different batches of vaccine. A batch prepared with a centrifugation step gave significantly higher geometric mean titres (16-fold increase over baseline) than did a batch in which there was a filtration step between fermentation and lyophilisation (10-fold increase over baseline). At a 5 x 10(9) CFU dose, CVD 103-HgR is well tolerated and highly immunogenic in Indonesian children and should therefore be further investigated for use as a one-dose live oral cholera vaccine in developing countries.

PIP: In February-March 1990, health workers administered a single dose of the oral cholera CVD 103 HgR vaccine with 5 x 100 million colony forming units (CFU), 5 x 10 million CFU, or 5 x 1 million CFU or of a placebo to 274 5-9 year old children in a village within the catchment area of the Infectious Diseases Hospital in North Jakarta, Indonesia. In September-October 1990, they gave a dose of the same vaccine containing either 5 x 1 billion CFU or 1 x 10 billion CFU from 1 of 2 different batches or a placebo (5 x 100 million inactivated Escherichia coli K 12) to 140 5-9 year old children. 70 children also received an extra dose of buffer. They conducted these trials to examine the safety, immunogenicity, and excretion of this live cholera vaccine. The higher dose genetically engineered oral cholera vaccine (5 x 1 billion CFU) resulted in higher seroconversion rates than the 5 x 100 million CFU vaccine which has 90% seroconversion rates among North American and European children (16% vs. 75-87% for 2 different batches). The centrifuged prepared vaccine resulted in significantly greater geometric mean titers (16-fold rise over baseline) than did the filtered prepared vaccine (10-fold rise over baseline) (p=.001). The extra buffer did not improve immunogenicity of CVD 10 HgR in these children. None of the 124 children who took the 5 x 1 billion or 1 x 10 billion CFU dose excreted the attenuated strain of Vibrio cholerae 01. Thus this recombinant vaccine strain would unlikely enter the environment or b transmitted to others. The frequency of adverse reactions was basically the same for the vaccine and the placebo. These results showed that the Indonesian children tolerated a single 5 x 1 billion dose of CVD 103 HgR well and induced considerable immunogenicity. Future studies using the same dose in 2-4 year old children are planned.