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

被引：13

作者：

McKelvie, Nicola D. ^{[1
]}

Khan, Shahid A. ^{[2
]}

Karavolos, Michail H. ^{[1
]}

Bulmer, David M. ^{[1
]}

Lee, Jeong Jin ^{[1
]}

DeMarco, Raquel ^{[1
]}

Maskell, Duncan J. ^{[2
]}

Zavala, Fidel

Hormaeche, Carlos E. ^{[1
,3
]}

Khan, C. M. Anjam ^{[1
]}

机构：

[1] Univ Newcastle, Sch Med, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[2] Univ Cambridge, Dept Clin Vet Med, Ctr Vet Sci, Cambridge CB2 1TN, England

[3] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA

来源：

FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY | 2008年 / 52卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

Salmonella; lipopolysaccharide; waaN; aroA; multivalent vaccine;

D O I：

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

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：237 / 246

页数：10