Genetic detoxification of anaroA Salmonella entericaserovar Typhimurium vaccine strain does not compromise protection against virulentSalmonellaand enhances the immune responses towards a protective malarial antigen

Article

Author: David M. Bulmer ; Nicola D. McKelvie ; Fidel Zavala ; Carlos E. Hormaeche ; Duncan J. Maskell ; Michail H. Karavolos ; Shahid A. Khan ; Raquel DeMarco ; Jeong Jin Lee ; C. M. Anjam Khan

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.

01 Mar 2000·Applied and Environmental Microbiology

Development of a Nonantibiotic Dominant Marker for Positively Selecting Expression Plasmids in Multivalent Salmonella Vaccines

Article

Author: Khan, C. M. Anjam ; Hormaeche, Carlos E. ; McNeill, Hesta V. ; Sinha, Katharine A. ; Lee, Jeong Jin

ABSTRACT We report the novel application of a herbicide-resistance-based dominant marker for the positive selection of expression plasmids in Salmonella serovar vaccines. The β-lactamase gene of the plasmid pTETnir15, which expresses fragment C of tetanus toxin (TetC), has been replaced with the bar gene marker. The new plasmid pBAT1 can be positively selected in vitro within Salmonella serovars in the presence of the herbicide dl -phosphinothricin. The expression of TetC remains unaltered, and the Salmonella enterica serovar Typhimurium vaccine strain is stable and immunogenic in vivo.

100 Deals associated with Multivalent Salmonella vaccine (AchilleS Vaccines)

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Indication	Highest Phase	Country/Location	Organization	Date
Paratyphoid Fever	Preclinical	Italy	University of Cambridge	-
Paratyphoid Fever	Preclinical	United Kingdom	University of Cambridge	-
Paratyphoid Fever	Preclinical	United Kingdom	AchilleS Vaccines SRLStartup	-
Paratyphoid Fever	Preclinical	Italy	AchilleS Vaccines SRLStartup	-
Typhoid Fever	Preclinical	United Kingdom	AchilleS Vaccines SRLStartup	-
Typhoid Fever	Preclinical	Italy	University of Cambridge	-
Typhoid Fever	Preclinical	Italy	AchilleS Vaccines SRLStartup	-
Typhoid Fever	Preclinical	United Kingdom	University of Cambridge	-

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