Abstract
BackgroundDuring the development of a vaccine, identification of the correlates of protection is of paramount importance for establishing an objective criterion for the protective performance of the vaccine. However, the ascertainment of correlates of immunity conferred by any vaccine is a difficult task.MethodsWhile conducting a phase three double-blind, cluster-randomized, placebo-controlled trial of a bivalent killed whole-cell oral cholera vaccine in Kolkata, we evaluated the immunogenicity of the vaccine in a subset of participants. Randomly chosen participants (recipients of vaccine or placebo) were invited to provide blood samples at baseline, 14 days after the second dose and one year after the first dose. At these time points, serum geometric mean titers (GMT) of vibriocidal antibodies and seroconversion rates for vaccine and placebo arms were calculated and compared across the age strata (1 to 5 years, 5 to 15 years and more than 15 years) as well as for all age groups.ResultsOut of 137 subjects included in analysis, 69 were vaccinees and 68 received placebo. There were 5•7 and 5•8 geometric mean fold (GMF) rises in titers to Vibrio cholerae Inaba and Ogawa, respectively at 14 days after the second dose, with 57% and 61% of vaccinees showing a four-fold or greater titer rise, respectively. After one year, the titers to Inaba and Ogawa remained 1•7 and 2•8 fold higher, respectively, compared to baseline. Serum vibriocidal antibody response to V. cholerae O139 was much lower than that to Inaba or Ogawa. No significant differences in the GMF-rises were observed among the age groups.ConclusionsThe reformulated oral cholera vaccine induced a statistically significant anti-O1 Inaba and O1 Ogawa vibriocidal antibody response 14 days after vaccination, which although declined after one year remained significantly higher than baseline. Despite this decline, the vaccine remained protective five years after vaccination.
Highlights
The past decade has seen an increase in the number of cholera outbreaks worldwide [1]
Overall geometric mean-fold (GMF) rises in serum antibodies were lower in Kolkata (4.5-fold in adults and 12.6-fold in children) than that in SonLa (26.8-fold) where only adults participated
For responses against Inaba, a six-fold GMF rise from baseline was seen 14 days after the second dose, which declined to two-fold after one year
Summary
The past decade has seen an increase in the number of cholera outbreaks worldwide [1]. An inexpensive, killed oral cholera vaccine (OCV) was produced in Vietnam in 1997 following technology transfer from Sweden. Prior to the transfer of the technology to India, immunogenicity studies were first conducted in adults in SonLa, Vietnam (a cholera non-endemic area) [5] and in children and adults in Kolkata, India (a cholera endemic region) [5,6]. In SonLa, 90% of the vaccine recipients, aged 18–48 years, developed $ four-fold rise in vibriocidal antibodies to V. cholerae O1 Inaba, and there was a 26.8-fold rise in the geometric mean titers (GMT) 14 days after the second dose suggesting the reformulated vaccine was highly immunogenic. Overall geometric mean-fold (GMF) rises in serum antibodies were lower in Kolkata (4.5-fold in adults and 12.6-fold in children) than that in SonLa (26.8-fold) where only adults participated. The ascertainment of correlates of immunity conferred by any vaccine is a difficult task
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