Neisserial surface protein A (NspA) is currently being investigated with humans as a candidate vaccine for the prevention of meningococcal disease. Although NspA is highly conserved, the ability of anti-NspA antibodies to bind to or elicit complement-mediated bactericidal activity against diverse Neisseria meningitidis serogroup B strains is controversial. To evaluate strain differences in NspA surface accessibility and susceptibility to bactericidal activity, we prepared murine immunoglobulin G2a anti-NspA monoclonal antibodies (MAbs) and evaluated their functional activity against 10 genetically diverse N. meningitidis serogroup B strains. By colony Western blot, all 10 strains expressed NspA as detected by one or more MAbs. By flow cytometry, two MAbs were found to bind to the bacterial surface of 6 of the 10 strains. In addition, two strains showed variable NspA surface accessibility for the MAbs despite being uniformly positive for NspA expression by colony Western blotting. Only 4 of the 10 strains were susceptible to anti-NspA complement-mediated bacteriolysis. Passively administered MAb protected infant rats from developing bacteremia after challenge with N. meningitidis serogroup B strain 8047 (surface binding positive, susceptible to anti-NspA bacteriolysis), was poorly protective against strain BZ232 (surface binding variable, resistant to bacteriolysis), and did not protect against strain M986 (surface binding negative, resistant to bacteriolysis). Finally, NspA does not appear to be critical for causing bacteremia, as an NspA knockout from strain 8047 was highly virulent in infant rats. Taken together, these findings suggest that an NspA-based vaccine will need to incorporate additional antigens to elicit broad protection against N. meningitidis serogroup B.
Epidemiologic data on the etiologic organisms is important for appropriate empirical antibiotic treatment of bacterial meningitis. We identified the etiologies of community-acquired bacterial meningitis in Korean adults and the associated epidemiological factors. A retrospective, multicenter nationwide study was carried out. Patients 18 years of age or older with community-acquired bacterial meningitis with a confirmed pathogen were enrolled. Demographic, clinical, and microbiological data were collected. One hundred and ninety-five cases were collected. Streptococcus pneumoniae was the most common pathogen (50.8%), followed by Staphylococcus aureus (10.3%), Klebsiella pneumoniae (7.7%), Listeria monocytogenes (6.7%), and group B Streptococcus (3.1%). The penicillin resistance rate of the S. pneumoniae was 60.3%; 40.0% of the organisms were not susceptible to third-generation cephalosporins. The combination of third-generation cephalosporin with vancomycin was used in 76.3% of cases. Steroids were given before or with the first dose of antibiotics in 37.4% of patients. The 30-day mortality rate was 20.5% and neurological sequelae developed in 15.6% of cases. S. pneumoniae was the most common organism identified in community-acquired bacterial meningitis among Korean adults. S. aureus, K. pneumoniae, L. monocytogenes, and group B Streptococcus were also common. S. pneumoniae had high rates of resistance to penicillin and third-generation cephalosporins.
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