Comparison of alternative buffers for use with a new live oral cholera vaccine, Peru-15, in outpatient volunteers

Abstract

During development of Peru-15, a new live oral vaccine for cholera, the role of buffer needed to be evaluated. Generally, oral bacterial vaccines are acid labile and need to be administered by using a formulation which protects them from gastric acid. We compared three different buffers for use with Peru-15, including a standard bicarbonate-ascorbic acid buffer, Alka-Seltzer, and a new electrolyte-rice buffer, CeraVacx. Saline served as the control. Thirty-nine healthy adult volunteers received Peru-15 (10 8 CFU) with one of the three buffers or saline in a double-masked study. The volunteers were monitored for symptoms for 7 days after the dose, serum was tested for antibody responses by vibriocidal antibody and immunoglobulin G antitoxin enzyme-linked immunosorbent assays, and stool samples were tested for excretion of the vaccine strain. Side effects were minimal in all groups. All 30 volunteers who took Peru-15 with a buffer showed significant rises in vibriocidal antibody titer. The magnitude of the rises was higher in the CeraVacx group than in the other two buffer groups. Four of nine volunteers who took the vaccine with saline also showed increased titers, but they were lower than those in any of the three buffer groups. Excretion of the vaccine strain was similar in the buffer groups, but excretion was not associated with the magnitude of the vibriocidal responses. Excretion of Peru-15 was not detected in the saline group. We conclude that buffer does amplify the serological response to Peru-15 and that CeraVacx may provide benefits not provided by other buffers.

Peru-15 (Choleragarde®), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand

“…There were no additional solicited events reported during the day 7 to day 90 follow up period. However, the frequency of adverse events was low when compared with the earlier studies of Peru-15 from North America [11][12][13][14].…”

“…Peru-15 (Choleragarde®), a live attenuated OCV, is derived from a Peruvian strain of Vibrio cholerae O1, biotype El Tor by removing cholera toxin genetic elements and by reinserting the cholera toxin B subunit (ctxB) [11]. It has been evaluated in phase I and II clinical trials for its safety and immunogenicity in different age-groups in America and Bangladesh where Peru-15 was well tolerated and showed satisfactory immunogenicityat doses ranging from 1x10 7 to 1x10 9 Colony Forming Units; however, there is no such data in HIV-infected individuals (CFU) [11][12][13][14][15][16].…”

A study of different buffers to maximize viability of an oral Shigella vaccine

“…CeraVacx is a buffer specifically designed to neutralize gastric acidity during vaccine administration and was used during live oral cholera vaccine trials with vaccine candidate Peru-15 [21]. CeraVacx is composed of a defined form of rice syrup (long chain carbohydrates) with sodium bicarbonate and trisodium citrate.…”

A Phase 4, multicentre, randomized, single-blind clinical trial to evaluate the immunogenicity of the live, attenuated, oral rotavirus vaccine (116E), ROTAVAC®, administered simultaneously with or without the buffering agent in healthy infants in India

“… 3 The rationale for the inclusion of a buffer stems from the knowledge and experiences by manufacturers of RV and other oral live vaccines (cholera and typhoid). 6 , 7 , 16 , 21-23 In order to prevent degradation of the oral vaccine by acidic conditions of the stomach, buffering components were added in all such vaccine formulations. In view of all the above discussed issues including, 116E strain characteristics, conflicting literature reports on the role of buffer, 16-18 and programmatic considerations during the use of the vaccine, we have planned to specifically investigate the immunological characteristics (measured as anti-RV IgA) of the ORV 116E strain administered with and without a buffer.…”