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Human immune response to Pseudomonas aeruginosa mucoid exopolysaccharide (alginate) vaccine
G B Pier1, D DesJardin, M Grout
1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Abstract:
Chronic lung infection with mucoid Pseudomonas aeruginosa is the major pathologic feature of cystic fibrosis. Previous studies suggested that a failure to produce opsonic antibody to the mucoid exopolysaccharide (MEP; also called alginate) capsule is associated with the maintenance of chronic bacterial infection. Provision of MEP-specific opsonic antibodies has therapeutic potential. To evaluate the ability of MEP to elicit opsonic antibodies, humans were immunized with two lots of MEP vaccine that differed principally in molecular size. Lot 2 had a larger average MEP polymer size. Both vaccines were well tolerated, but lot 1 was poorly immunogenic, inducing long-lived opsonic antibodies in only 2 of 28 vaccinates given doses of 10 to 150 micrograms. In contrast, at the optimal dose of 100 micrograms, lot 2 elicited long-lived opsonic antibodies in 80 to 90% of the vaccinates. The antibodies elicited by both lots enhanced deposition of C3 onto mucoid P. aeruginosa cells and mediated opsonic killing of heterologous mucoid strains expressing distinct MEP antigens. These results indicate that the polymers of MEP with the largest molecular sizes safely elicit opsonic antibodies in a sufficiently large proportion of vaccinates to permit studies of active and passive immunization of cystic fibrosis patients against infection with mucoid P. aeruginosa.
Insights
A new vaccine using larger mucoid exopolysaccharide (MEP) polymers effectively elicits opsonic antibodies against Pseudomonas aeruginosa in cystic fibrosis patients. This finding supports further research into MEP-based immunotherapies for chronic lung infections.
Area of Science:
- Immunology
- Microbiology
- Pulmonary Medicine
Background:
- Chronic Pseudomonas aeruginosa lung infection is a hallmark of cystic fibrosis.
- Lack of opsonic antibodies to the mucoid exopolysaccharide (MEP) capsule contributes to persistent infection.
- MEP-specific opsonic antibodies offer potential therapeutic benefits.
Purpose of the Study:
- To assess the immunogenicity of MEP vaccines in humans.
- To determine if MEP molecular size influences antibody production.
- To evaluate the therapeutic potential of MEP-elicited antibodies.
Main Methods:
- Human immunization with two MEP vaccine lots differing in polymer size (Lot 1 vs. Lot 2).
- Assessment of vaccine tolerability and immunogenicity (opsonin production).
- Evaluation of antibody-mediated bacterial killing and complement deposition (C3).
Main Results:
- Both vaccines were well-tolerated.
- Lot 1 (smaller polymers) showed poor immunogenicity (2/28 responders).
- Lot 2 (larger polymers) elicited long-lived opsonic antibodies in 80-90% of subjects at 100 micrograms.
- Antibodies enhanced bacterial C3 deposition and opsonic killing of mucoid P. aeruginosa.
Conclusions:
- Larger molecular size MEP polymers safely and effectively elicit opsonic antibodies.
- The high response rate supports further investigation of MEP vaccines for cystic fibrosis patients.
- This research paves the way for active and passive immunization strategies against mucoid P. aeruginosa.