Complex Serology and Immune Response of Mice to Variant High-Molecular-Weight O Polysaccharides Isolated from Pseudomonas aeruginosa Serogroup O2 Strains

Abstract

The O antigen of the Pseudomonas aeruginosalipopolysaccharide is the optimal target for protective antibodies, but the unusual and complex nature of their sugar substituents has made it difficult to define the range of these structures needed in an effective vaccine. Most clinical isolates of P. aeruginosacan be classified into 10 O-antigen serogroups, but slight chemical differences among O polysaccharides within a serogroup give rise to subtype epitopes. These epitopes could impact the reactivity of O-antigen-specific antibodies, as well as the susceptibility of a target strain to protective, opsonic antibodies. To define parameters of serogroup and subtype-epitope immunogenicity, antigenicity, and surface expression on P. aeruginosa cells, we prepared high-molecular-weight O-polysaccharide vaccines from strains ofP. aeruginosa serogroup O2, for which eight structurally variant O antigens expressing six defined subtype epitopes (O2a to O2f) have been identified. A complex pattern of immune responses to these antigens was observed following vaccination of mice. The high-molecular-weight O polysaccharides were generally more immunogenic at low doses (1 and 10 μg) than at a high dose (50 μg) and usually elicited antibodies that opsonized the homologous strain for phagocytic killing. Some of the individual polysaccharides elicited cross-opsonic antibodies to a variable number of strains that express all of the defined serogroup O2 subtype epitopes. Combination into one vaccine of two antigens that individually elicited cross-reactive opsonic antibodies to most members of the O2 serogroup inhibited, instead of enhanced, the production of antibodies broadly reactive with most serogroup O2 subtype strains. Thus, immune responses to P. aeruginosa O antigens may be restricted to a limited range of epitopes on structurally complex O antigens, and combining multiple related antigens into a single vaccine formulation may inhibit the production of those antibodies best able to protect against mostP. aeruginosa strains within a given O-antigen serogroup.

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

“…Nevertheless, several heterogeneous OPS-based P. aeruginosa serotypes are responsible for life-threatening infections, limiting the utility of monovalent vaccines. Consequently, a heptavalent version with different OPS serotypes was prepared; however, antagonistic reactions resulted in limited levels of opsonic antibodies being detected [229].…”

DsbM affects aminoglycoside resistance inPseudomonas aeruginosaby the reduction of OxyR

“…Pseudomonas aeruginosa is a common, opportunistic Gram‐negative pathogen that often causes serious infections in susceptible populations, such as hospital patients (Hatano & Pier, ; Carmel‐Harel & Storz, ). It has been reported that the incidence of clinical multidrug‐resistant P. aeruginosa infections has been climbing steadily year after year (Chang et al ., ; Lee et al ., ).…”

PilO of Pseudomonas aeruginosa 1244: subcellular location and domain assignment

“…As mentioned above, the glycan specificity for the pilin glycosylation reaction lies in the first sugar of the O-antigen repeating unit (Horzempa et al, 2006a), a saccharide that shows strong structural similarities among the O-antigens of P. aeruginosa (Hatano and Pier, 1998). This situation suggests that it might be possible to synthesize a low-molecular-weight molecule that would inhibit the glycosylation reaction, thereby preventing attachment of the O-antigen.…”