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Infection and Immunity, April 2003, p. 1650-1655, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1650-1655.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cross-Reactivity of Antibodies against PorA after Vaccination with a Meningococcal B Outer Membrane Vesicle Vaccine

C. L. Vermont,1,2* H. H. van Dijken,1 A. J. Kuipers,1 C. J. P. van Limpt,3 W. C. M. Keijzers,4 A. van der Ende,4 R. de Groot,2 L. van Alphen,1 and G. P. J. M. van den Dobbelsteen1

Laboratory for Vaccine Research,1 Laboratory for Clinical Vaccine Research, Netherlands Vaccine Institute (NVI), Bilthoven,3 Department of Pediatrics, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam,2 Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center (AMC)/RIVM, Amsterdam, The Netherlands4

Received 16 August 2002/ Returned for modification 24 September 2002/ Accepted 19 December 2002

The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and PorA-identical patient isolates were compared as a target in SBA, to ensure that the vaccine strains are representative for patient isolates. Geometric mean titers (GMTs) in SBA against patient isolates with subtypes P1.5-2,10 and P1.5-1,2-2 after vaccination with HexaMen were generally lower than those against vaccine strains with the same subtype, although the percentage of vaccine responders (>=4-fold increase in SBA after vaccination) was not affected. Using various P1.7-2,4 patient isolates, GMTs as well as the number of vaccine responders were higher than for the P1.7-2,4 vaccine strain, indicating that the use of the P1.7-2,4 vaccine strain may have underestimated the immunogenicity of this subtype in HexaMen. Secondly, the cross-reactivity of antibodies induced by MonoMen and HexaMen was studied using several patient isolates that differed from the vaccine subtypes by having minor antigenic variants of one variable region (VR), by having a completely different VR or by having a different combination of VRs. MonoMen induced P1.4-specific antibodies that were cross-reactive with P1.4 variants P1.4-1 and P1.4-3. HexaMen induced a broader cross-reactive antibody response against various patient isolates with one VR identical to a vaccine subtype or a combination of VRs included in HexaMen. Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2. The extended cross-reactivity of vaccinee sera induced by HexaMen against antigenic variants has important favorable implications for meningococcal B OMV vaccine coverage.

* Corresponding author. Mailing address: Laboratory for Vaccine Research, Netherlands Vaccine Institute, P.O. Box 457, 3720 AL Bilthoven, The Netherlands. Phone: 31 30 274 2931. Fax: 31 30 274 4429. E-mail: c.vermont{at}erasmusmc.nl.

Editor: J. N. Weiser

Infection and Immunity, April 2003, p. 1650-1655, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1650-1655.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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