University of Iowa Research Foundation

University of California

Wyeth Holdings Corporation

Rasappa Arumugham

Michael A Apicella

Bradford W Gibson

Na-Gyong Lee

Melvin G Sunshine

Maria Fortuna-Nevin

A method is provided for identifying, isolating, and producing htrB mutants of gram-negative bacterial pathogens. The method comprises mutating the htrB gene of a gram-negative bacterial pathogen so that there is a lack of a functional htrB protein, resulting in a mutant that lacks one or more secondary acyl chains contained in the wild type gram-negative bacterial pathogen, and displays substantially reduced toxicity as compared to the wild type strain. Also, the present invention provides methods for using a vaccine formulation containing the htrB mutant, the endotoxin isolated therefrom, or the endotoxin isolated therefrom which is then conjugated to a carrier protein, to immunize an individual against infections caused by gram-negative bacterial pathogens by administering a prophylactically effective amount of the vaccine formulation.

Non-toxic mutants of pathogenic gram-negative bacteria

Antigenic conjugates are provided which comprise a carrier protein covalently bonded to the conserved portion of a lipopolysaccharide of a gram negative bacteria, wherein the conserved portion of the lipopolysaccharide comprises the inner core and lipid A portions of the lipopolysaccharide, the conjugate eliciting a cross reactive immune response against heterologous strains of the gram negative bacteria.

Antigenic conjugates of conserved lipopolysaccharides of gram negative bacteria

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Pittsford, NY, United States of America

Rasappa Arumugham