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National Vaccine Program Office
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Proposal Number: | N19 |
PI Name: | Zollinger, Wendell D. |
PI Email: | |
PI Title: | Chief |
Project Title: | Production and evaluation of a clinical lot of meningococcal native outer membrane vesicle vaccine prepared from a strain with genetically detoxified lipopolysaccharide |
Project Start: | 2003 |
Project End: | 2004 |
Abstract: Considerable progress has been made toward the development of a meningococcal group B vaccine based on the outer membrane proteins and lipopolysaccharide. One of the challenges in preparing such a vaccine is removal or detoxification of the tightly associated LPS (endotoxin) without altering the conformation or surface exposure of the membrane proteins. We have prepared a vaccine consisting of native outer membrane vesicles (NOMV) from a strain with genetically detoxified LPS. We hypothesize that this vaccine, which is prepared without exposure to detergent or denaturing agents, will be safe for parenteral administration and will allow presentation of the outer membrane proteins and LPS in their natural conformation and membrane environment. Development lots of genetically detoxified NOMV vaccine have been prepared and shown to be safe and immunogenic in mice and rabbits. A clinical lot of vaccine is being prepared from strain 44/76 ΔsynX ΔlpxL2 in order to evaluate this vaccine in human volunteers. The specific objectives of this proposal are to: 1) complete the cGMP manufacture (vialing) of the clinical lot of vaccine, 2) complete preclinical testing of the vaccine for safety and immunogenicity in mice and rabbits (FY03), and 3) conduct a phase I clinical study to evaluate the vaccine in human volunteers (FY04). Successful completion of the clinical study will provide an assessment of the effectiveness of this unique and promising vaccine approach.
Institution: Department of Defense
Date: July 2003
Last revised: January 13, 2004
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