Immunogenic properties of Pseudomonas aeruginosa mucoid exopolysaccharide

Abstract

Previous studies have shown that antibodies to Pseudomonas aeruginosa mucoid exopolysaccharide (MEP) can be divided into two types on the basis of their functional activity. One type is able to mediate opsonic killing in conjunction with leukocytes and complement, and the other type is not. We investigated, in mice, the properties of this antigen associated with elicitation of opsonic killing antibody. We found that smaller-sized material (KaV = 0.26), which has been tested as a human vaccine, elicited opsonic killing antibody in mice at low doses (1 to 10 ,ug) and at doses of .40 ,ug, only nonopsonic killing antibody was produced. A similar dose effect was seen with heat-killed mucoid P. aeruginosa cells. After immunization with high doses of this MEP or the heat-killed cells, the mice were refractory to induction of opsonic killing antibody no matter what dose of MEP was used as a booster. In contrast, a larger-molecular-weight preparation (Kav = 0.05) elicited opsonic killing antibody over a wide dose range (1 to 400 ,ug). Additionally, 50 ,ug of the larger-sized preparation could overcome the suppression induced by 50 ,ig of the smaller material. Suppression elicited by 50 ,ug of the smaller

Synthesis and characterization of Pseudomonas aeruginosa alginate–tetanus toxoid conjugate

“…In contrast to the result found here, Theilacker et al (2003) did not report the induction of opsonic antibodies in mice after their immunization with native alginate. A possible explanation for these conflicting results may be the different composition of the alginate preparations used in the two studies: the alginate antigens differed in K d , the ratio of mannuronic acid to guluronic acid, and acetate content (Garner et al, 1990).…”

Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia.

“…When alginate is used in high doses (but not in low doses) for immunization in mice, it elicits CD3 ϩ CD8 ϩ major histocompatibility complex-unrestricted cytotoxic T cells that selectively kill hybridomas producing opsonic but not nonopsonic antibodies (345). This cytotoxic activity, which is dependent on the presence of immune complexes, may explain the finding that the dose and size of alginate polymer used for immunization studies in mice or human volunteers may be critical parameters determining whether an immunization protocol will elicit opsonic or nonopsonic antibodies (138,339). Furthermore, mitogen activity of alginate (73), in combination with a similar activity of other Pseudomonas antigens, e.g., LPS, may contribute to the hypergammaglobulinemia associated with clinical deterioration in CF (340,470).…”

Immunological evaluation of an alginate‐based conjugate as a vaccine candidate against Pseudomonas aeruginosa

“…Therefore, we conjugated a strong and safe carrier protein to alginate by optimizing the conjugation process. We purified high molecular‐weight alginate because previous studies showed that the high molecular size could elicit an antibody response against alginate .…”

“…Several studies showed that alginate elicits opsonic antibodies and has conserved epitopic sites in the most mucoid strains . The safety of alginate has been proven at various dosages by some human trials , and a direct relationship between the molecular size of alginate and the induction of opsonic antibodies has been observed . In spite of the safety of alginate as a vaccine candidate to confer immunity against P. aeruginosa infection, it does not have sufficient immunogenicity to provoke long‐lived opsonic antibodies .…”