Elsevier

Vaccine

Volume 25, Issue 2, 4 January 2007, Pages 231-238
Vaccine

Peru-15, a live attenuated oral cholera vaccine, is safe and immunogenic in Bangladeshi toddlers and infants

https://doi.org/10.1016/j.vaccine.2006.08.031Get rights and content

Abstract

A live oral Vibrio cholerae O1 El Tor vaccine, Peru-15 was tested in a double-blind, randomized placebo controlled study for safety and immunogenicity in Phase I and Phase II studies in 240 Bangladeshi children aged 9 months–5 years of age. Two different doses (2 × 107 and 2 × 108 cfu) were tested. Vaccination did not elicit adverse events and the strain was genetically stable. Vibriocidal antibody responses developed in 42/50 (84%) toddlers (2–5 years) and 35/50 (70%) of younger children (9–23 months) and overall 77/100 (77%) who received the high dose. LPS-IgA-antibody responses were seen in 60% of toddlers and 34% of infants; 40% responded with IgA antibodies to cholera toxin. The responses to the reduced dose was lower. These studies demonstrate that Peru-15 at a dose of 2 × 108 cfu is safe and immunogenic in children in Bangladesh.

Introduction

A single dose, easily administered vaccine that can confer protection from cholera is needed for both children and adults in developing countries. One candidate, Peru-15 is a live oral vaccine that is based on an attenuated mutant of a Vibrio cholerae O1, El Tor Inaba strain. The vaccine has been found to be safe, immunogenic, and efficacious in North American volunteers [1], [2], [3] and safe and immunogenic in Bangladeshi adults [4]. Peru-15 genetically engineered to be non-toxinogenic and non-recombinational. It is non-motile and ctxB positive [2] and genetically stable [1], [4]. Since the vaccine is immunogenic in Bangladeshi and naïve North American volunteers it may likewise be immunogenic in children who have not been primed with V. cholerae O1. After satisfactory immunogenicity and safety studies in adults [4], we initiated studies in descending age groups from toddlers to infants 9 months of age to evaluate safety, immunogenicity and excretion of the vaccine strain in Phase I/Phase II studies in Bangladesh.

Section snippets

Study participants

The study participants were children from an urban slum in the Mirpur area in Dhaka city in Bangladesh. The inpatient facility was adjacent to the ICDDR,B hospital. The outpatient facility was at the Mirpur field site, in an urban neighborhood about 10 km from the ICDDR,B and participants were recruited from an area of about 1 km around this facility.

Eligibility

Inclusion criteria included being healthy, aged between 5 years and 9 months of age. Exclusion criteria included any chronic disease, or any recent

Adverse events to Peru-15

Of the 240 children, 119 were male and 121 were female; 120 were in the 2–5 years range (toddlers) and 120 were 9–23 months of age range (infants) (Table 2). The vaccine was well tolerated in both age groups in the inpatient and outpatient phases (Table 3). The surveillance for side-effects revealed only mild symptoms, and occurred in similar rates in subjects receiving vaccine and placebo. Complaints of headache, vomiting and abdominal cramp were observed in only a few children. There was no

Discussion

This is the first report of the testing of Peru-15 in the pediatric group. A single dose of 2 × 108 cfu was found to be safe in both the toddlers and infants. A lower dose of 2 × 107 was much less immunogenic. Both the seroconversion rate and the magnitude of response to the full dose were appreciable.

Of the different advantages of Peru-15, one was the almost complete lack of reactogenicity when doses of 2 × 107 or 2 × 108 cfu were evaluated. Adverse events attributable to the vaccine were not detected.

Acknowledgements

This work was supported by the Diseases of the Most Impoverished Program, funded by the Bill and Melinda Gates Foundation and coordinated by the International Vaccine Institute (Grant No. C-5).

References (24)

  • F. Qadri et al.

    Increased levels of inflammatory mediators in children and adults infected with Vibrio cholerae O1 and O139

    Clin Diagn Lab Immunol

    (2002)
  • S.H. Lee et al.

    Selection for in vivo regulators of bacterial virulence

    Proc Natl Acad Sci USA

    (2001)
  • Cited by (0)

    1

    Peru-15 study group in the laboratory, clinical and field sites and other collaborators.

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