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

Abstract

In a phase 4, randomized, placebo-controlled, double-blind, multicenter study, to assess the safety and immunogenicity of live, attenuated cholera vaccine PXVX0200 in children aged 2–5 years in the United States, 172 volunteers were randomized 6:1 to receive a single dose of 1 × 109 colony forming units (CFU) of PXVX0200 or placebo. Immunogenicity endpoints included serum vibriocidal antibody (SVA) levels on days 1, 11, and 29. Safety was assessed by comparing solicited signs and symptoms on days 1–8, unsolicited adverse events through day 29, and serious adverse events (SAEs) through day 181. The SVA seroconversion rates 10 days after immunization were 98.1% and 0% in vaccine and placebo recipients, respectively, and the vaccine seroconversion rate was non-inferior to the 93.5% rate seen in the bridging population of adults aged 18–45 years from a lot consistency study. Most reactogenicity was mild to moderate, and there were no study-related SAEs. PXVX0200 appears safe and immunogenic in children aged 2–5 years.

Parenteral Vaccination with a Cholera Conjugate Vaccine Boosts Vibriocidal and Anti-OSP Responses in Mice Previously Immunized with an Oral Cholera Vaccine

“…The vaccine is highly immunogenic and is approved for use in individuals aged 2–64 years in the United States. 4 , 22 , 43 , 44 The U.S. version of the vaccine has not yet been evaluated for protection in areas endemic for cholera; however, the vaccine has been shown to provide at least short-term protection in North American adult volunteers challenged 30 days (90% vaccine efficacy) or 90 days (79% vaccine efficacy) after vaccination. 22 No data regarding protective efficacy in children, or duration of protection beyond 90 days postvaccination, are currently available.…”

Cholera Vaccine: Recommendations of the Advisory Committee on Immunization Practices, 2022

“…In clinical trials conducted using the current formulation, no vaccine-related serious adverse events were reported among participants aged 2–64 years ( 27 , 29 – 31 ). In clinical trials among adults aged 18–45 years, solicited adverse events were more commonly reported by CVD 103-HgR recipients than by placebo (i.e., buffer alone) recipients ≤7 days after vaccination and included tiredness (31.3% versus 27.4%; mostly mild or moderate), headache (28.9% versus 23.6%; mostly mild), nausea or vomiting (18.3% versus 15.2%; mostly mild), and diarrhea (3.9% versus 1.2%; mostly mild) ( 31 , 35 ).…”

“…ACIP used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the certainty of evidence for selected benefits and harms prespecified by each work group (Table 1) (26). For both age groups, ACIP considered evidence regarding safety and immunogenicity of the available formulation of CVD 103-HgR (27)(28)(29)(30)(31). For adults aged 18-64 years, ACIP also considered evidence regarding the efficacy of the current formulation of CVD 103-HgR (data were limited to adults aged 18-45 years) and evidence regarding efficacy and safety of the previously available formulation of CVD 103-HgR (2,32).…”

“…No studies directly assessed vaccine efficacy among children and adolescents aged 2–17 years; only immunogenicity data were available. In both adults aged 18–64 years and children and adolescents aged 2–17 years, the current formulation of CVD 103-HgR induced serum vibriocidal antibody seroconversion (a fourfold or more rise in titer) in >93% of recipients on day 11 ( 27 , 29 – 31 ).…”

“…In the clinical trials among children and adolescents aged 2–17 years, any solicited adverse event ≤7 days after vaccination was reported by 55.1% of vaccine recipients and 50.7% of placebo recipients. Solicited adverse events more commonly reported by vaccine than placebo recipients aged 2–17 years included tiredness (35.7% versus 30.7%; mostly mild), headache (27.4% versus 25.3%; mostly mild), abdominal pain (27.8% versus 18.7%; mostly mild), and lack of appetite (21.4% versus 14.7%; mostly mild) ( 27 , 29 , 35 ).…”