Palatability, reactogenicity and immunogenicity of engineered live oral cholera vaccine CVD 103-HgR in Chilean infants and toddlers

Background. Live oral cholera vaccine CVD 103-HgR is well-tolerated and imm unogenic when administered to adults, school age children and preschool chi ldren in a single 5 x 10(9) colony-forming unit dose. Because elicitation o f immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to inve stigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age. Methods, The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102), One- half of the subjects were randomly allocated to receive vaccine and the oth er one-half to receive placebo, in double blind fashion, After 2 weeks of d ouble blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 we eks after each dosing. The buffered vaccine "cocktail" had a volume of 100 ml; subjects who ingested 170 ml were considered fully vaccinated. Findings. Only 37% of subjects overall (25% of 3- to 5-month-olds) ingested 170 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion o f vaccine vs. placebo. Seroconversion after ingestion of a single dose of C VD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%), Of subjects who ingested two doses,5 of 118 excreted vaccine organisms on Day 7 after the f irst dose vs. 0 of 118 after the second dose, Interpretation. Single dose oral CVD 103-HgR is well-tolerated and immunoge nic in infants even when a partial dose is ingested. The buffered vaccine c ocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immun izing infants must be sought.