Journal
VACCINE
Volume 28, Issue 21, Pages 3679-3687Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2010.03.019
Keywords
Live Salmonella vaccine; Paratyphi; Reactogenicity; Rabbit model
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Eight Salmonella enterica serovar Paratyphi A strains were screened as candidates to create a live attenuated paratyphoid vaccine. Based on biochemical and phenotypic criteria, four strains, RKS2900. MGN9772, MGN9773 and MGN9779, were selected as progenitors for the construction of Delta phoPQ mutant derivatives. All strains were evaluated in vitro for auxotrophic phenotypes and sensitivity to deoxycholate and polymyxin B. All Delta phoPQ mutants were more sensitive to deoxycholate and polymyxin B than their wild-type progenitors, however MGN10028, MGN10044 and MGN10048, required exogenous purine for optimal growth. Purine requiring strains had acquired point mutations. in purB during strain construction. All four mutants were evaluated for reactogenicity and immunogenicity in an oral rabbit model. Three strains were reactogenic in a dose-dependent manner, while one strain, MGN10028, was well-tolerated at all doses administered. All Delta phoPQ strains were immunogenic following a single oral dose. The in vitro profile coupled with the favorable reactogenicity and immunogenicity profiles render MGN10028 a suitable live attenuated Paratyphi A vaccine candidate. (C) 2010 Elsevier Ltd. All rights reserved.
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