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Clinical and Vaccine Immunology, October 2008, p. 1598-1605, Vol. 15, No. 10
1071-412X/08/$08.00+0     doi:10.1128/CVI.00192-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Hyperproliferation of B Cells Specific for a Weakly Immunogenic PorA in a Meningococcal Vaccine Model{triangledown}

Thomas A. Luijkx,* Jacqueline A. M. van Gaans-van den Brink, Harry H. van Dijken, Germie P. J. M. van den Dobbelsteen, and Cécile A. C. M. van Els

Department of Vaccine Research, Unit for Research and Development, Netherlands Vaccine Institute, Antonie van Leeuwenhoeklaan 11, 3721 MA Bilthoven, The Netherlands

Received 28 May 2008/ Returned for modification 4 July 2008/ Accepted 22 August 2008

Highly homologous meningococcal porin A (PorA) proteins induce protective humoral immunity against Neisseria meningitidis group B infection but with large and consistent differences in the levels of serum bactericidal activity achieved. We investigated whether a poor PorA-specific serological outcome is associated with a limited size of the specific B-cell subpopulation involved. The numbers of PorA-specific splenic plasma cells, bone marrow (BM) plasma cells, and splenic memory B cells were compared between mice that received priming and boosting with the weakly immunogenic PorA (P1.7-2,4) protein and those that received priming and boosting with the highly immunogenic PorA (P1.5-1,2-2) protein. Immunoglobulin G (IgG) titers (except at day 42), bactericidal activity, and the avidity of IgG produced against P1.7-2,4 were significantly lower at all time points after priming and boosting than against P1.5-1,2-2. These differences, however, were not associated with a lack of P1.7-2,4-specific plasma cells. Instead, priming with both of the PorAs resulted in the initial expansion of comparable numbers of splenic and BM plasma cells. Moreover, P1.7-2,4-specific BM plasma cells, but not P1.5-1,2-2-specific plasma cells, expanded significantly further after boosting. Likewise, after a relative delay during the priming phase, the splenic P1.7-2,4-specific memory B cells largely outnumbered those specific for P1.5-1,2-2, upon boosting. These trends were observed with different vaccine formulations of the porins. Our results show for the first time that B-cell subpopulations involved in a successfully maturated antibody response against a clinically relevant vaccine antigen are maintained at smaller population sizes than those associated with poor affinity maturation. This bears consequences for the interpretation of immunological memory data in clinical vaccine trials.

* Corresponding author. Present address: Bacteriological R and D, Nobilon Schering-Plough, P.O. Box 320, 5830 AH Boxmeer, The Netherlands. Phone: 31 485 587779. Fax: 31 485 585345. E-mail: Thomas.Luijkx{at}SP.Nobilon.com

{triangledown} Published ahead of print on 3 September 2008.

Clinical and Vaccine Immunology, October 2008, p. 1598-1605, Vol. 15, No. 10
1071-412X/08/$08.00+0     doi:10.1128/CVI.00192-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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