Immunization of cystic fibrosis patients with a Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine.
Healthy, non-colonized cystic fibrosis (CF) patients (N = 26) were immunized with an octavalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. Vaccination was well tolerated and induced anti-lipopolysaccharide (LPS) antibodies of a high affinity capable of promoting the opsonophagocytic killing of P. aeruginosa by human peripheral lymphocytes. In contrast, anti-LPS antibodies acquired after natural infection possessed a very low affinity and were non-opsonic. To determine if immunization could prevent or delay infections due to P. aeruginosa, the infection rate among immunized patients was compared retrospectively to age and gender-matched controls. After 6 years of clinical follow-up, 15/20 (75%) of control and 8/23 (35%) of immunized subjects were classified as infected (p = 0.022). The persistence of high-affinity antibodies among immunized patients correlated with a significantly lower rate of infection after 4-6 years of observation. Infection of immunized patients was correlated with a dramatic decline in total antibody titer between year 2 and 3 of follow-up. Smooth, typeable strains of P. aeruginosa predominated among immunized patients. In contrast, rough, nontypeable strains were most frequently isolated from nonimmunized patients. Mucoid P. aeruginosa strains were isolated from 6 nonimmunized patients versus only I immunized subject.
Cryz
S J
SJ
Swiss Serum and Vaccine Institute, Berne, Switzerland.
Lang
A
A
Rüdeberg
A
A
Wedgwood
J
J
Que
J U
JU
Fürer
E
E
Schaad
U
U
D036002:ADP Ribose Transferases; D000293:Adolescent; D000328:Adult; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D005098:Exotoxins / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007223:Infant; D008214:Lymphocytes / Q000276:immunology / Q000382:microbiology; D019081:O Antigens / Q000276:immunology*; D010587:Phagocytosis; D011552:Pseudomonas Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D014614:Vaccines, Synthetic; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D005098:Exotoxins; D019081:O Antigens; D014614:Vaccines, Synthetic; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A