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

Maria Rosario Z Capeding, Maria Liza Antoinette M Gonzales, Mandeep Singh Dhingra, Naveena Aloysia D'Cor, Venkat Jayanth Midde, Badri Narayan Patnaik, Yaël Thollot, Eric Desauziers, Maria Rosario Z Capeding, Maria Liza Antoinette M Gonzales, Mandeep Singh Dhingra, Naveena Aloysia D'Cor, Venkat Jayanth Midde, Badri Narayan Patnaik, Yaël Thollot, Eric Desauziers

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: Shanchol; The Philippines; cholera vaccine; immunogenicity; safety.

Figures

Figure 1.
Figure 1.
Flow of participants through the study. Visit 1 (Day 0), Visit 2 (D14), Visit 3 (D28), Visit 4 (D44) and study completion. Blood samples were drawn at Visit 1, 2 and 3 (n=112 at Visit 1, 2, and 3 for ages 1–4 and 5–14 years; n=112 at Visit 1 and 2, and n=111 at Visit 3 for ≥15 years).
Figure 2.
Figure 2.
Vibriocidal antibody titers and proportion of participants with a ≥ 4-fold rise from baseline (seroconversion) (full analysis set).

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