Notes on a talk given at the Annual CFRI Conference by Anna Rüdeberg, M.D.
Anna Rüdeberg, M.D., University of Bern Hospital, Switzerland, and IACFA Medical Advisor, has been a part of an exciting study in Switzerland to determine the effects of a vaccine on Pseudomonas aeruginosa, a bacterial infection that is a major factor in the endobronchial inflammatory process for patients with CF. Most patients with CF become colonized with P. aeruginosa between the ages of eight and 20. The aim of her study was to test the hypothesis that vaccination of CF patients not colonized with P. aeruginosa would delay colonization of their airways. Her study focuses on the effects of the introduction of antibodies to P. aeruginosa, lipopolysaccharide (LPS), a special molecule of the P. aeruginosa cell membrane.
The study included 26 patients with CF who had no prior history of infection with P. aeruginosa. These patients were immunized with an octavelent O-polysaccharide-toxin A (O-PS-TA) conjugate vaccine. After an initial dose, a second dose was administered at two months, a third at 12 months, and once a year every year thereafter. After the third application, there was a booster reaction, that is, a large number of antibodies (an immune or protective protein) were present. During the four years after the initial dose, 16 patients (or 61.5 percent of the group) remained free of P. aeruginosa infection, while ten (or 38.5 percent) became infected. The total serum anti-LPS antibody levels in infected patients caused by the immunization vaccine were comparable to the levels in non-infected patients. However, in contrast, 12 of the 16 non-infected patients versus three of the ten infected patients mounted and maintained a high affinity, anti-LPS antibody response. A high affinity of antibodies here means that the antibodies are characterized by a special and qualitatively higher or greater attraction for the P. aeruginosa bacterium. The vaccinated patients were compared, in retrospect, to a group of age- and gender-matched, non-immunized, non-colonized CF patients. The rate at which patients acquired P. aeruginosa infections was significantly lower among the group of immunized versus non-immunized patients during two years of observation. Subsequently, only those immunized patients who maintained a high affinity anti-LPS antibody response had a significant reduction in the rate of infection over three years with four strains of P. aeruginosa cultured. Naturally acquired antibodies (without the vaccine) showed low opsonic affinity, low attraction to P. aeruginosa, and impaired effector function, whereas vaccine-induced antibodies showed at least 100-fold greater affinity and better effector function.
Dr. Rüdeberg concluded that there was no deterioration of the effects of the vaccine, no side effects, 60 percent of the patients were able to generate substantial amounts of the high-affinity antibodies, and high-affinity, anti-LPS antibodies can protect against P. aeruginosa colonization. The vaccine studies encourage further efforts in the direction of slowing down colonization with the P. aeruginosa bacterium.
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