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Genetic detoxification of an aroA Salmonella enterica serovar Typhimurium vaccine strain does not compromise protection against virulent Salmonella and enhances the immune responses towards a protective malarial antigen

Lookup NU author(s): Nicola McKelvie, Dr Michail Karavolos, Dr David Bulmer, Dr Jeong-Jin Lee, Professor Carlos Hormaeche, Dr Anjam Khan

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Abstract

Live Salmonella vaccines are limited in use by the inherent toxicity of the lipopolysaccharide. The waaN gene encodes a myristyl transferase required for the secondary acylation of lipid A in lipopolysaccharide. A waaN mutant exhibits reduced induction of the inflammatory cytokines associated with lipopolysaccharide toxicity. Here the characteristics of a Salmonella enterica serovar Typhimurium aroA waaN mutant (SK100) in vitro and in vivo compared with its parent aroA strain (SL3261) were described. Phenotypic analysis of purified lipopolysaccharide obtained from SK100 confirmed that the physical and biological activities of the lipopolysaccharide had been altered. Nevertheless both strains had similar patterns of colonization and persistence in mice and significantly the aroA waaN mutant was equally as effective as the parent at protecting against challenge with wild-type S. Typhimurium. Furthermore, a SK100 strain was constructed expressing both tetanus toxin fragment C and the circumsporozoite protein of a malaria parasite. In marked contrast to its isogenic parent, the new attenuated strain induces significantly enhanced immune responses against the circumsporozoite protein. The waaN mutation enhances the ability of this strain to elicit immune responses towards guest antigens. This study provides important insights into the development of safe and effective multivalent Salmonella vaccines. © 2008 Federation of European Microbiological Societies.

Publication metadata

Author(s): McKelvie ND, Khan SA, Karavolos MH, Bulmer DM, Lee JJ, DeMarco R, Maskell DJ, Zavala F, Hormaeche CE, Anjam Khan CM

Publication type: Article

Publication status: Published

Journal: FEMS Immunology and Medical Microbiology

Year: 2008

Volume: 52

Issue: 2

Pages: 237-246

ISSN (print): 0928-8244

ISSN (electronic): 1574-695X

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1574-695X.2007.00368.x

DOI: 10.1111/j.1574-695X.2007.00368.x

PubMed id: 18177343

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