Immunogenic and antigenic properties of a heptavalent high-molecular-weight O-polysaccharide vaccine derived from Pseudomonas aeruginosa

Abstract

We investigated the chemical and immunologic properties of a heptavalent vaccine composed of high-molecular-weight polymers of the lipopolysaccharide (LPS) O polysaccharides representative of the most common clinical isolates of Pseudomonas aeruginosa. We also evaluated the serum antibody response to nonvaccine strains of P. aeruginosa, including strains expressing structural variants (subtype strains) of the O side chain of the vaccine strains. The polyvalent vaccine, prepared under conditions suitable for human use, contained low levels of contaminants and passed preclinical safety and toxicity tests required for human use. Chemical analyses indicated that individual polysaccharides were composed of both O-side chain and core sugars. Following immunization of C3H/HeN mice and New Zealand White rabbits, antibody titers against vaccine components increased between 32- and 200-fold. Antibodies reactive with LPS isolated from smooth and rough nonvaccine strains were also elicited. Analysis of the opsonic activity against the known LPS subtype variants of the vaccine strains revealed a variable pattern of killing, which ranged from opsonic killing of > or = 69% of bacterial cells representing all subtype variants within a serogroup to opsonization of only a minority of the subtype variant strains. Mouse and rabbit immune sera showed different patterns of opsonic activity against subtype strains, indicating that different epitopes on these antigens are immunodominant in the representatives of these two animal species tested. The polyvalent vaccine was effective at eliciting antibodies to vaccine components in mice and rabbits, but it remains to be determined if the current heptavalent formulation contains sufficient components to provoke human antibodies reactive with a majority of clinical strains of P. aeruginosa.