title: A study of different buffers to maximize viability of an oral Shigella vaccine.
abstract: Live, whole cell killed and subunit vaccines are being developed for diarrheal diseases caused by V. cholerae, Shigella species, ETEC, and Campylobacter. Some of these vaccines can be administered orally since this route best mimics natural infection. Live vaccines administered orally have to be protected from the harsh acidic gastric environment. Milk and bicarbonate solutions have been administered to neutralize the stomach acid. For many Shigella vaccine trials, 100-120 ml of a bicarbonate solution is ingested followed by the live vaccine candidate, which is delivered in 30 ml of bicarbonate, water or saline. It is not clear if maximum bacterial viability is achieved under these conditions. Also, volumes of neutralizing buffer that are optimal for adults may be unsuitable for children and infants. To address these questions, we performed studies to determine the viability and stability of a Shigella sonnei vaccine candidate, WRSS1, in a mixture of different volumes of five different buffer solutions added to hydrochloric acid to simulate gastric acidity. Among the buffers tested, bicarbonate solution, rotavirus buffer and CeraVacx were better at neutralizing acid and maintaining the viability of WRSS1. Also, a much smaller volume of the neutralizing buffer was sufficient to counteract stomach acid while maintaining bacterial viability.
authors.affiliation: Bacterial Diseases Branch, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Chandrasekaran
authors.affiliation: PATH, Enteric Vaccines Initiative, Seattle, WA, USA.
authors.forename: Manjari
authors.initials: M
authors.lastname: Lal
authors.affiliation: PATH, Enteric Vaccines Initiative, Seattle, WA, USA.
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Van De Verg
authors.affiliation: Bacterial Diseases Branch, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: malabi.m.venkatesan.civ@mail.mil.
authors.forename: Malabi M
authors.initials: MM
authors.lastname: Venkatesan
mesh_terms: D000284:Administration, Oral; D002021:Buffers; D004355:Drug Stability; D006801:Humans; D006851:Hydrochloric Acid / Q000633:toxicity; D050296:Microbial Viability / Q000187:drug effects*; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*; D012764:Shigella sonnei / Q000187:drug effects* / Q000276:immunology*
chemical_list: D002021:Buffers; D022281:Shigella Vaccines; D006851:Hydrochloric Acid
keywords: Acid neutralization buffer; S. sonnei vaccine; Vaccine viability; WRSS1 vaccine