Enzyme-linked immunosorbent assay to evaluate the immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine in humans

Abstract

A highly sensitive enzyme-linked immunosorbent assay was developed for Klebsiella capsular polysaccharide (CPS) and used to evaluate the immunoglobulin G (IgG) antibody response to a 24-valent CPS vaccine in seven adult volunteers. The median rise in titer to all vaccine antigens in samples from the volunteers was significant (twofold or greater). Significant IgG responses to 11 immunologically related serotypes not included in the vaccine were also noted. The mean cross-reacting IgG titer of 127.2 was only slightly lower than the mean titer of 175.7 to the serotypes in the vaccine (P < 0.05). The mean 29.9-fold increase in titer to the serotypes in the vaccine was significantly higher than the mean 13.5-fold increase in titer to the additional antigens (P < 0.001). The difference was partly because of the significantly lower (P < 0.01) natural antibody titers in the preimmune sera to the serotypes in the vaccine, compared with those to serotypes not included in the vaccine. The selection of vaccine serotypes was based on the frequency of serotype isolation from cases of Klebsiela bacteremia. The above findings, which show low levels of natural antibody to these serotypes, support the hypothesis that anti-CPS antibody is protective against bacteremic disease.

Immunological Principles and Emerging Strategies of Vaccination for the Elderly

“…Since most fatal gram negative bacillary infections are caused by Escherichia coli, Pseudotnonas aeruginosa and Klebsiella species, it would be useful to have some form of immunoprophylaxis specific to these organisms. To this end, investigators have recently constructed protein conjugate vaccines to the O‐polysaccharides of E. coli and P. aeruginosa , as well as a multivalent Klebsiella capsular polysaccharide vaccine 225 – 227 . Each of these preparations is immunogenic in humans, and may ultimately be useful both for active immunization of high risk individuals as well as for preparation of hyperimmune gammaglobulin from immunized healthy individuals.…”

Proinflammatory Cytokines in AntilipopolysaccharideImmunity Against Klebsiella Infections

“…The obstacle for the successful preparation of such K-antigen-based immunologic tool is the fact that there are more than 70 K antigens expressed on clinical isolates, most of them present in 1%–2% of clinical strains [ 12 , 13 ]. Indeed, Cryz and coworkers developed a K-antigen-based vaccine containing purified polysaccharides of 24 capsular serotypes [ 14 , 15 ]. A hyperimmune intravenous immunoglobulin (Ig) preparation made from the postvaccination plasma of volunteers immunized simultaneously with the Klebsiella K antigen and Pseudomonas vaccines has undergone a randomized clinical trial with intensive care patients [ 16 ].…”

O-antigen seroepidemiology of Klebsiella clinical isolates and implications for immunoprophylaxis of Klebsiella infections

“…The fact that pulmonary and bloodstream infections caused by klebsiellae result in high rates of mortality despite the use of potent antimicrobial agents (3,27) has acted as a stimulus to researchers to develop immunologic strategies for their prevention and treatment. Since it has been shown that the Klebsiella capsule (K antigen) plays an important role in pathogenicity (12,41), Cryz and coworkers developed a capsular antigen-based vaccine containing the purified polysaccharides of 24 capsular serotypes (7,15). A hyperimmune intravenous immunoglobulin (Ig) preparation made from the postvaccination plasma of volunteers immunized simultaneously with the Klebsiella capsular antigen and Pseudomonas vaccines has recently undergone a randomized clinical trial with intensive-care patients (9).…”