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.

Suman Kanungo,Bandana Sen,Dilip Mahalanabis,Gaurav Goel,Mihir Kumar Bhattacharya,Puja Jhunjhunwala,Thandavarayan Ramamurthy,Dipika Sur,Byomkesh Manna,Ranjan K Nandy,Goutam Chowdhury,Bindu Dey,Thungapathra M,Hemanta Koley,Amit Ghosh,Sanjay Gupta,Gururaja P Pazhani,G Balakrish Nair

doi:10.1371/journal.pone.0099381

Abstract

BackgroundA 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.MethodA 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.ResultThe 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.ConclusionThis 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 RegistrationClinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2012/04/002582

Highlights

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
This study demonstrates that VA 1.4 at a single dose of 1.96109 is safe and immunogenic in adults from a cholera endemic region
Two types of killed oral cholera vaccine are currently available, (i) Dukoral based on formalin and heat-killed whole cells of V. cholerae O1 plus recombinant cholera toxin B subunit, given with a bicarbonate buffer, and (ii) Shanchol and mORCVAX, the two identical vaccines formulated by two different manufactures based on V. cholerae serogroups O1 and O139

Summary

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). Anti-cholera toxin antibody was detected in very few recipients of the vaccine

Conclusion

Methods

Results

Immune Response

Discussion