Vaccination responses to capsular polysaccharides of Neisseria meningitidis and Haemophilus influenzae type b in two C2-deficient sisters: Alternative pathway-mediated bacterial killing and evidence for a novel type of blocking IgG

Meningitis caused by Neisseria meningitidis serogroup W-135 was diagnosed i n a 14-year-old girl with a history of neonatal septicemia and meningitis c aused by group B streptococci type III. C2 deficiency type I was found in t he patient and her healthy sister. Both sisters were vaccinated with tetrav alent meningococcal vaccine and a conjugate Haemophilus influenzae type b v accine. Three main points emerged from the analysis. First, vaccination res ulted in serum bactericidal responses demonstrating anticapsular antibody-m ediated recruitment of the alternative pathway. Second, addition of C2 to p revaccination sera produced bactericidal activity in the absence of anticap sular antibodies, which suggested that the bactericidal action of antibodie s to subcapsular antigens detected in the sera might strictly depend on the classical pathway. A third point concerned a previously unrecognized type of blocking activity. Thus, postvaccination sera of the healthy sister cont ained IgG that inhibited killing of serogroup W-135 in C2-deficient serum, and the deposition of C3 on enzyme-linked immunosorbent assay plates coated with purified W-135 polysaccharide. Our findings suggested blocking to be serogroup-specific and dependent on early classical pathway components. Ret ained opsonic activity probably supported postvaccination immunity despite blocking of the bactericidal activity. The demonstration of functional vacc ination responses with recruitment of alternative pathway-mediated defense should encourage further trial of capsular vaccines in classical pathway de ficiency states.