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Clin. Vaccine Immunol. doi:10.1128/CVI.00341-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Immunity to Neisseria meningitidis Group B in Serum Bactericidal-Negative Adults

Children's Hospital Oakland Research Institute, Oakland, CA 94609

^* To whom correspondence should be addressed. Email: dgranoff{at}chori.org.

	Abstract

Serum complement-mediated bactericidal antibody (SBA) remains the serologic hallmark of protection against meningococcal disease despite experimental and epidemiologic data that SBA may underestimate immunity. We measured bactericidal activity against three strains of N. meningitidis group B in sera from 48 healthy adults, and in whole blood from 15 subjects. Blood was anti-coagulated with lepirudin, a specific thrombin inhibitor not known to activate complement. Depending on the test strain, protective SBA titers 1:4 were present in only 8 to 15 percent of the subjects as compared with 40 to 87 percent with the blood assay. Among SBA-negative subjects, blood from 23 to 42 percent gave a decrease of 2 log₁₀ CFU/ml after one-hour incubation, and 36 to 83 percent gave a decrease of 1 log₁₀ after two hours. For most blood samples, bactericidal antibodies were primarily directed against non-capsular antigens since activity was not inhibited by group B polysaccharide. For some SBA-negative subjects, white cells were not needed since similar respective bactericidal activity was observed in blood and plasma. Bactericidal activity by whole blood of SBA-negative subjects can be rapid (<1 hr) and effective (2 log₁₀) and, among all subjects, was 4- to 6-fold more prevalent than a positive SBA. Thus, while a SBA titer 1:4 predicts protection against meningococcal disease, a titer <1:4 is poorly predictive of susceptibility. More sensitive assays than SBA are needed to assess protective meningococcal immunity or we risk underestimating the extent of immunity in the population and effectiveness of new meningococcal vaccines.

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