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Infection and Immunity, November 2003, p. 6367-6371, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6367-6371.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Relative Immunogenicity of PorA Subtypes in a Multivalent Neisseria meningitidis Vaccine Is Not Dependent on Presentation Form

Thomas A. Luijkx,^* Harry van Dijken, Hendrik-Jan Hamstra, Betsy Kuipers, Peter van der Ley, Loek van Alphen, and Germie van den Dobbelsteen

Laboratory for Vaccine Research, Netherlands Vaccine Institute, 3720 AL Bilthoven, The Netherlands

Received 23 April 2003/ Returned for modification 30 May 2003/ Accepted 12 August 2003

The hexavalent meningococcal vaccine HexaMen, containing six PorAs on two vesicles, was tested in clinical studies. Although fourfold increases in serum bactericidal activity (SBA) titers against all of the PorAs were observed, there were significant differences between PorA-specific SBA titers. SBA titers were mainly directed against one PorA from each vesicle, P1.5-2,10 and P1.5-1,2-2, and were lower against the other PorAs, especially P1.7-2,4 and P1.19,15-1. We investigated whether these differences were due to immunological interference that resulted in competition between the three PorAs on the same vesicle or whether they were caused by a difference in the immunogenicities of the separate PorAs. Therefore, mice were immunized either with HexaMen, with six monovalent outer membrane vesicles (OMVs) representing the same six PorAs simultaneously (HexaMix), or with only one of the monovalent OMVs. The immunoglobulin G and SBA titers after HexaMen immunization in mice resembled the results obtained in clinical studies. Although immunization with HexaMix gave higher titers than immunization with HexaMen for some PorAs, the pattern of high and low titers was the same. Similar differences in immunogenicity between subtypes were seen after monovalent immunization when interference was eliminated as a cause of the differences. Monovalent immunization resulted in higher titers for P1.5-1,2-2 and P1.7,16 than immunization with HexaMen. However, no significant differences were found for the weakly immunogenic PorAs, P1.7-2,4 and P1.19,15-1. Since immunization with the six PorAs in the trivalent presentation form (HexaMen) and in the mixture of monovalent vesicles (HexaMix) resulted in the same pattern of high and low titers, we concluded that the differences between the PorA-specific responses are due to differences in the immunogenicities of the various PorAs and not due to interference that results in competition between different PorAs.

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* Corresponding author. Mailing address: Laboratory for Vaccine Research, Netherlands Vaccine Institute (NVI), P.O. Box 457, 3720 AL Bilthoven, The Netherlands. Phone: 31 30 274 3999. Fax: 31 30 274 4429. E-mail: Thomas.luijkx{at}nvi-vaccin.nl.

Editor: J. N. Weiser

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Infection and Immunity, November 2003, p. 6367-6371, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6367-6371.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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