Update on CVD 103-HgR single-dose, live oral cholera vaccine

ABSTRACT

Cholera remains endemic in >50 countries, putting millions at risk, especially young children for whom killed vaccines offer limited protection. An oral, live attenuated vaccine – CVD 103-HgR (Vaxchora vaccine) – was licensed by the US FDA in 2016 for adults aged 18–64 years traveling to endemic regions, based on clinical trials in human volunteers showing the vaccine was well tolerated and conferred 90% efficacy within 10 days. The evidence base for Vaxchora vaccine has expanded with additional clinical trial data, in older adults (aged 46–64 years) and children (aged 2–17 years), demonstrating that the vaccine produces a strong vibriocidal antibody response. Over 68,000 doses have been administered in the United States, with no new safety signals. The dose volume has been reduced in children to improve acceptability, and cold chain requirements are less st ringent, at +2°C─+8°C. The vaccine has recently been licensed in the Untied States for children aged 2–17 years, in Europe for individuals aged ≥2 years, and for home administration in Europe. Next steps include a Phase 4 study in infants (6–23 months). Additional information is needed regarding duration of immunity, the need for and timing of revaccination, and efficacy data from lower-middle-income countries.

KEYWORDS:

• Attenuated vaccines
• cholera
• cholera vaccines
• clinical effectiveness
• expert opinion
• CVD 103-HgR
• vaxchora vaccine
• vibrio cholerae

Article highlights

• The live oral cholera vaccine, Vaxchora vaccine, was recently licensed in Europe for home administration in adults and children 2 years of age and older traveling to at-risk countries, while the age indication in the United States was recently expanded to include travelers 2-64 years of age.

• The Vaxchora vaccine dose volume has been reduced in children to improve acceptability, and cold chain requirements are now less stringent at +2°C to +8°C.

• Vaxchora vaccine induces SVA seroconversion in as little as 7 days and is 90% protective at 10 days and 80% protective at 90 days postvaccination against cholera challenge. The long-term duration of protection provided by Vaxchora vaccine is unknown and in need of further study.

• Vaxchora vaccine induces robust memory B-cell responses which last for at least 6 months, and there is a statistically significant association between vaccine-induced increases in LPS-specific IgA memory B cells and lower diarrheal stool volumes following challenge.

• Determination of the need for Vaxchora vaccine reimmunization is complicated by the presence of pre-existing SVA and the persistence of local gut immunity, which may interfere with colonization of the small bowel following a second dose of vaccine.

• While killed cholera vaccines have demonstrated efficacy in endemic and epidemic situations, they require multiple doses and provided limited protection after one dose, especially in children less than 5 years of age. Vaxchora vaccine might one day provide a useful alternative in at-risk infants and children – further study is needed.

Declaration of interest

J McCarty, PA de Lame, M Lock, and D Haney are paid consultants for Emergent Travel Health Inc. L Bedell and D Cassie are employees of Emergent Travel Health Inc. S Bennett is an employee of Adjuvance Technologies Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Medical writing assistance was provided by Elements Communications Ltd, funded by Emergent Biosolutions Inc.