HUMAN IMMUNE-RESPONSE TO PSEUDOMONAS-AERUGINOSA MUCOID EXOPOLYSACCHARIDE (ALGINATE) VACCINE

Chronic lung infection with mucoid Pseudomonas aeruginosa is the major pathologic feature of cystic fibrosis. Previous studies suggested tha t a failure to produce opsonic antibody to the mucoid exopolysaccharid e (MEP; also called alginate) capsule is associated with the maintenan ce of chronic bacterial infection. Provision of MEP-specific opsonic a ntibodies 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 larg er average MEP polymer size. Both vaccines were well tolerated, but lo t 1 was poorly immunogenic, inducing long-lived opsonic antibodies in only 2 of 28 vaccinates given doses of 10 to 150 mu g. In contrast, at the optimal dose of 100 mu g, lot 2 elicited long-lived opsonic antib odies in 80 to 30% of the vaccinates. The antibodies elicited by both lots enhanced deposition of C3 onto mucoid P. aeruginosa cells and med iated opsonic killing of heterologous mucoid strains expressing distin ct MEP antigens. These results indicate that the polymers of MEP with the largest molecular sizes safely elicit opsonic antibodies in a suff iciently large proportion of vaccinates to permit studies of active an d passive immunization of cystic fibrosis patients against infection w ith mucoid P. aeruginosa.