Safety and immunogenicity of the killed bivalent (O1 and O139) whole-cell cholera vaccine in the Philippines

ABSTRACT

The killed bivalent (O1 and O139) whole cell oral cholera vaccine (OCV) (Shanchol™) was first licensed in India in 2009 and World Health Organization pre-qualified in 2011. We assessed the safety and immunogenicity of this OCV in the Philippines. This was a phase IV, single-arm, descriptive, open-label study. We recruited 336 participants from 2 centers: 112 participants in each age group (1–4, 5–14 and ≥ 15 years). Participants received 2 OCV doses 14 d apart. Safety was monitored throughout the trial. Blood samples were collected at baseline (pre-vaccination) and 14 d after each dose. Serum vibriocidal antibody titers to V. cholerae O1 (El Tor Inaba and El Tor Ogawa) and O139 strains were assessed, with seroconversion defined as ≥ 4-fold increase from baseline in titers. No immediate unsolicited systemic adverse events/reactions were observed. Unsolicited systemic adverse events were mostly grade 1 intensity. One serious adverse event occurred after the first dose, but was unrelated to vaccination. High seroconversion rates (range 69–92%) were achieved against the O1 serotypes with a trend toward higher rates in the 1–4 y (86–92%) and 5–14 y (86–88%) age groups than the ≥ 15 y age group (69–83%). Lower seroconversion rates were achieved against the O139 serotype (35–70%), particularly in those aged ≥ 15 y (35–42%). The 2-dose regimen of the killed bivalent whole cell OCV was well-tolerated in this study conducted in the Philippines, a cholera-endemic country. Robust immune responses were observed even after a single-dose.

KEYWORDS:

• cholera vaccine
• immunogenicity
• Shanchol
• safety
• The Philippines

Disclosure of potential conflicts of interest

MRZC received a research grant from Sanofi Pasteur. MLAMG received personal fees from Sanofi Pasteur during the conduct of the study, and personal fees and non-financial support from Sanofi Pasteur outside the submitted work (including honoraria for lectures, participation in speakers' bureaus and travel grants to attend medical conferences). MSD was an employee of the vaccine manufacturer (Shantha Biotechnics Private Limited) at the time of the study conduct and is currently an employee of Sanofi Pasteur. NAD'C, VJM, BNP are employees of Shantha Biotechnics Private Limited, and YT and ED employees of Sanofi Pasteur.

Acknowledgments

The authors thank all the volunteers who participated in the study. Authors also thank Anvar Rasuli, Karina Abalos, Marie-Claude Bonnet and Martin Dupuy for their valuable contribution to the study. Editorial assistance with the preparation of the manuscript was provided by Juliette Gray of inScience Communications, Springer Healthcare, funded by Sanofi Pasteur.

Funding

Funding for this study was provided by Sanofi Pasteur.