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Clinical and Vaccine Immunology, December 2007, p. 1596-1602, Vol. 14, No. 12
1071-412X/07/$08.00+0     doi:10.1128/CVI.00341-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Immunity to Neisseria meningitidis Group B in Adults despite Lack of Serum Bactericidal Antibody{triangledown}

Jo Anne Welsch and Dan Granoff*

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

Received 7 August 2007/ Returned for modification 18 September 2007/ Accepted 27 September 2007

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 Neisseria meningitidis group B in sera from 48 healthy adults and in whole blood from 15 subjects. Blood was anticoagulated with lepirudin, a specific thrombin inhibitor not known to activate complement. Depending on the test strain, protective SBA titers of ≥1:4 were present in only 8 to 15% of the subjects, whereas bactericidal activity was present in 40 to 87% of subjects according to the blood assay. Among SBA-negative subjects, blood from 23 to 42% gave a decrease of ≥2 log10 CFU/ml after 1 h of incubation, and blood from 36 to 83% gave a decrease of ≥1 log10 after 2 h. For most blood samples, bactericidal antibodies primarily were directed against noncapsular antigens, since activity was not inhibited by group B polysaccharide. For some SBA-negative subjects, white cells were not needed, since similar respective bactericidal activities were observed in blood and plasma. Bactericidal activity by whole blood of SBA-negative subjects can be rapid (<1 h) and effective (≥2 log10) and, among all subjects, was four- to sixfold more prevalent than a positive SBA. Thus, while an SBA titer of ≥1:4 predicts protection against meningococcal disease, a titer of <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 the effectiveness of new meningococcal vaccines.

* Corresponding author. Mailing address: 5700 Martin Luther King Jr. Way, Oakland, CA 94609. Phone: (510) 450-7640. Fax: (510) 450-7915. E-mail: dgranoff{at}chori.org

{triangledown} Published ahead of print on 3 October 2007.

Clinical and Vaccine Immunology, December 2007, p. 1596-1602, Vol. 14, No. 12
1071-412X/07/$08.00+0     doi:10.1128/CVI.00341-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Plested, J. S., Welsch, J. A., Granoff, D. M. (2009). Ex Vivo Model of Meningococcal Bacteremia Using Human Blood for Measuring Vaccine-Induced Serum Passive Protective Activity. CVI 16: 785-791 [Abstract] [Full Text]  
  • Moe, G. R., Bhandari, T. S., Flitter, B. A. (2009). Vaccines Containing de-N-Acetyl Sialic Acid Elicit Antibodies Protective against Neisseria meningitidis Groups B and C. J. Immunol. 182: 6610-6617 [Abstract] [Full Text]  
  • Granoff, D. M., Welsch, J. A., Ram, S. (2009). Binding of Complement Factor H (fH) to Neisseria meningitidis Is Specific for Human fH and Inhibits Complement Activation by Rat and Rabbit Sera. Infect. Immun. 77: 764-769 [Abstract] [Full Text]  
  • Beernink, P. T., Welsch, J. A., Bar-Lev, M., Koeberling, O., Comanducci, M., Granoff, D. M. (2008). Fine Antigenic Specificity and Cooperative Bactericidal Activity of Monoclonal Antibodies Directed at the Meningococcal Vaccine Candidate Factor H-Binding Protein. Infect. Immun. 76: 4232-4240 [Abstract] [Full Text]  
  • Beernink, P. T., Granoff, D. M. (2008). Bactericidal Antibody Responses Induced by Meningococcal Recombinant Chimeric Factor H-Binding Protein Vaccines. Infect. Immun. 76: 2568-2575 [Abstract] [Full Text]  
  • Plested, J. S., Granoff, D. M. (2008). Vaccine-Induced Opsonophagocytic Immunity to Neisseria meningitidis Group B. CVI 15: 799-804 [Abstract] [Full Text]  


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