Effect of cirrhosis on the production and efficacy of pneumococcal capsular antibody in a rat model.
We sought to study the immunogenicity of Type 3 pneumococcal capsular polysaccharide (PCP) antigen and the protective efficacy of Type 3 PCP antibodies in a rat model of cirrhosis. Cirrhosis with ascites was induced in male Sprague-Dawley rats by weekly gavage with CCl4. Cirrhotic and age-matched control rats were vaccinated with 25 micrograms of Type 3 PCP. Serum antibodies against Type 3 PCP were determined before vaccination and on postvaccination Days 5, 7, 10, 14, 21, 28, and 42 by radioimmunoassay. Maximum concentrations occurred at 7 days in cirrhotic rats and 10 to 14 days in control rats. Geometric mean Type 3 PCP antibody levels (ng AbN/ml) were higher in cirrhotic versus control rats before vaccination (75.9 versus 33.8; p = 0.011) and on post-vaccination Day 5 (626 versus 158; p = 0.008) and Day 7 (1,755 versus 493; p = 0.002). Postvaccination antibody from immunized control and cirrhotic animals provided passive immunity to Type 3 Streptococcus pneumoniae infection in mouse protection studies. Sham-immunized and PCP-immunized control and cirrhotic rats were challenged with 10(7) cfu Type 3 S. pneumoniae. Immunization was associated with a greater reduction in postchallenge mortality in control rats (91% reduced to 36%; p = 0.02) compared with cirrhotic rats (100% reduced to 83%; p = 1.0). Thus, the increased serum concentrations of functional, type-specific anticapsular antibody in vaccinated cirrhotic rats does not reverse their impaired resistance to Type 3 pneumococcal pneumonia.
Preheim
L C
LC
Infectious Diseases Section, Department of Veterans Affairs Medical Center, Creighton University School of Medicine, NE.
Mellencamp
M A
MA
Snitily
M U
MU
Gentry
M J
MJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D001428:Bacterial Vaccines; D004797:Enzyme-Linked Immunosorbent Assay; D008106:Liver Cirrhosis, Experimental / Q000276:immunology*; D008297:Male; D022242:Pneumococcal Vaccines; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D022242:Pneumococcal Vaccines