Evaluation of Peru‐15, a New Live Oral Vaccine for Cholera, in Volunteers

Abstract

A new live oral cholera vaccine, Peru-15, was studied for safety, immunogenicity, and excretion in 2 groups of healthy volunteers. Twelve inpatient volunteers received freshly harvested vaccine in doses of either 10(7) or 10(9) cfu. Subsequently 50 outpatient volunteers received freeze-dried vaccine in doses of 10(8) or 10(9) cfu or placebo in a three-cell, double-masked, placebo-controlled trial. The strain was well tolerated at all dose levels, and it stimulated high levels of vibriocidal antibodies in most inpatient volunteers and in all outpatient volunteers. Although antitoxin responses were less frequent and of lower magnitude than the vibriocidal responses, antitoxin responses were seen in >60% of the outpatient volunteers. About 60% of the volunteers excreted the vaccine in their feces; however, fecal excretion did not correlate with serologic responses. It is concluded that Peru-15 is a safe and immunogenic oral vaccine for cholera.

Randomized, Controlled Human Challenge Study of the Safety, Immunogenicity, and Protective Efficacy of a Single Dose of Peru-15, a Live Attenuated Oral Cholera Vaccine

“…These observations are consistent with the immunogenicity profiles and the lack of significant side effects in previous studies involving 85 subjects who ingested various doses of Peru-15 (7,12,13). In a controlled study (7), freshly harvested Peru-15 (2 ϫ 10 8 CFU) was administered to 11 volunteers.…”

“…In another set of studies (12), two groups of six inpatient volunteers received freshly harvested vaccine in doses of either 10 7 or 10 9 CFU. Loose stools were the most common side effect, but only one volunteer met the definition of diarrhea.…”

“…Loose stools were the most common side effect, but only one volunteer met the definition of diarrhea. In the same study, 50 outpatient volunteers received freeze-dried vaccine in doses of 10 8 or 10 9 CFU or placebo in a three-cell, double-masked, placebo-controlled trial (12). Side effects included diarrhea in two volunteers.…”

“…Possibly because it closely resembles natural infection, a singledose, live oral recombinant vaccine has the potential for generating both rapid onset of immunity and durable protection without subsequent booster doses. Therefore, two live recombinant oral vaccines (7,(11)(12)(13)16) have been developed. The availability of a safe, immunogenic vaccine that would provide a high level of long-term protection to those at high risk for illness would be highly desirable.…”

Safety and Immunogenicity of Escalating Dosages of a Single Oral Administration of Peru-15 pCTB, a Candidate Live, Attenuated Vaccine against Enterotoxigenic Escherichia coli and Vibrio cholerae

“…The parent strain Peru-15 has been found to be safe and immunogenic in Ͼ400 subjects, including North American adults (11,(14)(15)(16) and Bangladeshi adults (12) and children (13). We demonstrated that a single oral dose of Peru-15 pCTB was without significant reactogenicity or toxicity at dosages up to 10 10 CFU.…”