Safety and immunogenicity of a live oral recombinant cholera vaccine VA1.4: a randomized, placebo controlled trial in healthy adults in a cholera endemic area in Kolkata, India

PLoS One. 2014 Jul 1;9(7):e99381. doi: 10.1371/journal.pone.0099381. eCollection 2014.

Abstract

Background: A live oral cholera vaccine VA 1.4 developed from a non-toxigenic Vibrio cholerae O1 El Tor strain using ctxB gene insertion was further developed into a clinical product following cGMP and was evaluated in a double-blind randomized placebo controlled parallel group two arm trial with allocation ratio of 1∶1 for safety and immunogenicity in men and women aged 18-60 years from Kolkata, India.

Method: A lyophilized dose of 1.9×109 CFU (n = 44) or a placebo (n = 43) reconstituted with a diluent was administered within 5 minutes of drinking 100 ml of a buffer solution made of sodium bicarbonate and ascorbic acid and a second dose on day 14.

Result: The vaccine did not elicit any diarrhea related adverse events. Other adverse events were rare, mild and similar in two groups. One subject in the vaccine group excreted the vaccine strain on the second day after first dose. The proportion of participants who seroconverted (i.e. had 4-folds or higher rise in reciprocal titre) in the vaccine group were 65.9% (95% CI: 50.1%-79.5%) at both 7 days (i.e. after 1st dose) and 21 days (i.e. after 2nd dose). None of the placebo recipients seroconverted. Anti-cholera toxin antibody was detected in very few recipients of the vaccine.

Conclusion: This study demonstrates that VA 1.4 at a single dose of 1.9×109 is safe and immunogenic in adults from a cholera endemic region. No additional benefit after two doses was seen.

Trial registration: Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2012/04/002582.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antibodies, Bacterial / immunology
  • Cholera / immunology
  • Cholera / prevention & control*
  • Cholera Vaccines / administration & dosage*
  • Cholera Vaccines / adverse effects
  • Cholera Vaccines / immunology
  • Dose-Response Relationship, Immunologic
  • Female
  • Humans
  • India
  • Male
  • Middle Aged
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology
  • Vibrio cholerae*

Substances

  • Antibodies, Bacterial
  • Cholera Vaccines
  • Vaccines, Synthetic

Grants and funding

This vaccine was developed in three research laboratories of the Government of India and was not driven by the industry. The Department of Biotechnology of the Ministry of Science and Technology (DBT), Government of India was the lead agency that funded the project. (DBT) contracted Shantha Biotechnics Private Limited, Hyderabad, India to develop the vaccine into a clinical product (IP) for the present study. DBT, Ministry of Science and Technology, Government of India supported this project through a research grant to Society for Applied Studies, Kolkata. Sanjay Gupta and Gaurav Goel from the Catalyst Clinical Services Pvt. Ltd were contracted by DBT and used part of their salary to fund this study. The lead organization, Society for Applied studies (SAS), received a research grant from DBT and Bandana Sen a Research Fellow of SAS was financially supported from this grant. The funders and their contractors had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.