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Clinical and Vaccine Immunology, November 2007, p. 1451-1457, Vol. 14, No. 11
1071-412X/07/$08.00+0     doi:10.1128/CVI.00195-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Comparison of Phenotypically Indistinguishable but Geographically Distinct Neisseria meningitidis Group B Isolates in a Serum Bactericidal Antibody Assay{triangledown}

Jamie Findlow,1* Ann Holland,1 Nick Andrews,2 Vincent Weynants,3 Franklin Sotolongo,4 Paul Balmer,1 Jan Poolman,3 and Ray Borrow1

Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Laboratory, Manchester Medical Microbiology Partnership, P.O. Box 209, 2nd Floor, Clinical Sciences Building II, Manchester Royal Infirmary, Manchester, M13 9WZ,1 Health Protection Agency, Centre for Infections, Colindale, London, NW9 5EQ, United Kingdom,2 GlaxoSmithKline Biologicals, Rixensart, Belgium,3 Finlay Institute, Ave 27N. 19085, La Lisa A P 160017, Cod 11600, Havana, Cuba4

Received 10 May 2007/ Returned for modification 6 July 2007/ Accepted 9 September 2007

The "gold standard" assay for measuring serologic protection against Neisseria meningitidis group B (MenB) is the serum bactericidal antibody (SBA) assay. Of vital importance to the outcome of the SBA assay is the choice of the target strain(s), which is often chosen on the basis of phenotype or genotype. We therefore investigated the effect on the results produced by the SBA assay of using phenotypically indistinguishable but geographically distinct MenB isolates. Nine PorA P1.19,15 and 11 PorA P1.7-2,4 MenB isolates were incorporated into the SBA assay using human complement and were assayed against sera obtained either before or after outer membrane vesicle vaccination. Large differences in the results produced by the isolates in the SBA assay were demonstrated. These included differences as great as 5.8-fold in SBA geometric mean titers and in the proportions of subjects with SBA titers of ≥4. Ranges of as many as 9 SBA titers were achieved by individual sera across the panels of isolates. To determine the reasons for the differences observed, investigations into the expression of capsular polysaccharide, PorA, PorB, Opc, and lipooligosaccharide (LOS) and into LOS sialylation were completed. However, minor differences were found between strains, indicating similar expression and no antigen masking. These results have implications for the choice of MenB target strains for inclusion in future studies of MenB vaccines and highlight the requirement for standardization of target strains between laboratories.


* Corresponding author. Mailing address: Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Laboratory, Manchester Medical Microbiology Partnership, P.O. Box 209, 2nd floor, Clinical Sciences Building II, Manchester Royal Infirmary, Manchester, M13 9WZ, United Kingdom. Phone: 44 (0) 161 276 5697. Fax: 44 (0) 161 276 6792. E-mail: jamie.findlow{at}hpa.org.uk

{triangledown} Published ahead of print on 19 September 2007.


Clinical and Vaccine Immunology, November 2007, p. 1451-1457, Vol. 14, No. 11
1071-412X/07/$08.00+0     doi:10.1128/CVI.00195-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.