Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children and Adolescents Aged 6–17 Years

Abstract

The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, redeveloped as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera-induced diarrhea in adult volunteer challenge trials but has not been studied in children in developed countries. We performed a phase 4, placebo-controlled, double-blind, multicenter study to assess the safety, immunogenicity, and tolerability of a single, oral dose of PXVX0200 in children and adolescents aged 6-17 years in the United States and bridged immunogenicity to adults aged 18-45 years from a separate lot consistency study. Volunteers were randomized to receive a single dose of 1 × 10 9 colony forming units (CFU) of PXVX0200 or placebo. Immunogenicity endpoints included SVA levels on days 1, 11, and 29 in volunteers aged 6-17 years and also on days 91 and 181 in volunteers aged 12-17 years. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events (AEs) through day 29, and serious AEs through day 181. A total of 374 participants were enrolled, comprising 321 vaccine and 53 placebo recipients. The SVA seroconversion rates 10 days after immunization were 98.6% and 2.1% in vaccine and placebo recipients, respectively, and the vaccine seroconversion rate was non-inferior to the 93.5% rate seen in adults aged 18-45 years. Most reactogenicity was mild to moderate, and there were no vaccine-related serious AEs. The complete dose was consumed in 95.3% and 98.1% of vaccine and placebo recipients, respectively. PXVX0200 appears safe, immunogenic, and well tolerated in children and adolescents aged 6-17 years.

Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children Aged 2–5 Years in the United States

“…5 Because previous studies in children in developing countries of CVD 103-HgR suggested that the immune response, as measured by serum vibriocidal antibody (SVA) seroconversion rates and geometric mean titers (GMTs), was lower than the response in adults, a pediatric trial of PXVX0200 in children was recently performed in the United States. [8][9][10] In this study, CVD 103-HgR was shown to be safe, immunogenic, and well tolerated in children and adolescents aged 6-17 years. 10 Here, we report for the first time the safety and immunogenicity results from cohort 3 of that study, that is, children aged 2-5 years.…”

“…[8][9][10] In this study, CVD 103-HgR was shown to be safe, immunogenic, and well tolerated in children and adolescents aged 6-17 years. 10 Here, we report for the first time the safety and immunogenicity results from cohort 3 of that study, that is, children aged 2-5 years.…”

“…This was less than the 99.4% and 93.7% of vaccine recipients in the 12-to 17-and 6-to 11-yearold cohorts, respectively, who consumed ³ 80% of the dose. 10 Taste was ranked as very good, good, or neutral by the caregivers of 91 (62.3%) and 18 (69.2%) of Vaxchora and placebo recipients, respectively. Optional Pure Via Stevia sweetener was added to all, but one, of the doses; thus, assessment of its effect on palatability was not possible.…”

“…Study methods have been previously described and were similar for cohort 3, except that palatability was assessed by the caregiver instead of the subject. 10 The study was performed in children aged 2-5 years at eight U.S. sites from July 2017 through September 2019. For serum antibody assays, blood was collected from all participants on days 1, 11, and 29.…”

“…5,11 In this study, GMT and GMFI at day 11 were lower than those seen in cohorts 1 and 2 and the adult bridging study, possibly reflecting immunologic or intestinal immaturity in the youngest cohort. 6,10 However, because seroconversion rates were similar and SVA seroconversion is the best correlate of protection against moderate to severe diarrhea, it is hoped that because challenge studies cannot be performed in children, the efficacy of PXVX0200 in the youngest cohort would be similar to the efficacy in adults.…”