ead to higher titers of natural antibodies. Since IFA stimulates Thl lymphocytes to produce the cytokines interleukin 2, gamma interferon, and tumor necrosis factor beta, this may explain the developing antibody level seen in these rats. The pathologic INNO-406 changes observed in the D ALG toxin Aand P. aeruginosa alginate immunized animals were similar in degree, the total clearance of the bacteria in the two groups was also similar. However, the doses and composition of the two alginates used for immunization were rather different. Rats immunized with depolymerized alginate received two 25,ug doses, whereas rats immunized with purified alginate received 140 jig per dose.
Although we did not investigate the opsonic capacity of sera in this study, our findings do not seem to be in agreement with those of Pier et al, who found that mice and rats immunized with 1 to 10 jig of MEP, ON-01910 respectively, elicited opsonizing antibodies, which reduced the chronic lung infection and induced complete bacterial clearance compared with the results in nonimmune controls. However, doses of. 40,ug per mouse and 100,ug per rat induced only nonopsonic antibodies, resulting in more severe lung damage and more animals with detectable P. aeruginosa in the lungs, when compared with results for animals immunized with low doses. Furthermore, it was found that in mice, a higher molecular weight preparation of MEP elicited opsonic killing antibodies over a wide dose range. We have no obvious explanation for the differences between our results and those of Pier et al.
Woods and Bryan immunized rats twice with 100 jig of alginate and showed that animals inoculated with a nonmucoid strain cleared the bacteria whereas the rats inoculated with a mucoid strain remained infected on day 30. These findings are also different from ours, since we found that rats immunized with either 140 jig of purified alginate or 25 jig of depolymerized alginate were able to clear the mucoid challenge strain. The severity of the pathologic changes observed in our rats immunized with alginate could be due to hypersensitivity reactions, e. g, immune complexes formed during the chronic lung infection, as suggested by Woods and Bryan. LPS was included in two of the vaccines used in the study, the O PS toxin A conjugate and the P. aeruginosa sonicate. The number of cross reactive IgM, IgG, and IgA antibodies elicited by the toxin A conjugate against PAO 579 LPS was small.
Considering the 0 antigens involved, this is surprising since two of the eight serotypes represented in the vaccine have a similar 0 group 2/5 to that of the antigen used in the ELISA, and we would therefore expect a certain cross reactivity. The low level of cross reacting antibodies could be due to differences in the typing antisera and typing methods, which may lead to apparently similar Habs 0 groups with antigenically different LPS types. The O PS toxin A conjugate vaccine has previously been used in a clinical study of noncolonized CF patients. It is thoughtprovoking that the antibody responses are low in rats whereas the vaccine induces high and functional antibody levels when used in humans. When rats were immunized with a combination of the two toxin A conjugate vaccines, diminished immune responses were recorded against all antigen