Previous Article | Next Article 
Infection and Immunity, November 2009, p. 5080-5089, Vol. 77, No. 11
0019-9567/09/$08.00+0 doi:10.1128/IAI.00701-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Immunoproteomic Analysis of the Development of Natural Immunity in Subjects Colonized by Neisseria meningitidis Reveals Potential Vaccine Candidates
,
Jeannette N. Williams,1
Paul J. Skipp,2
C. David O'Connor,2
Myron Christodoulides,1 and
John E. Heckels1*
Molecular Microbiology, Division of Infection, Inflammation and Immunity, University of Southampton Medical School, Southampton General Hospital, Southampton SO16 6YD, United Kingdom,1 Centre for Proteomic Research and School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, United Kingdom2
Received 22 June 2009/ Returned for modification 22 July 2009/ Accepted 28 August 2009
The potential protective effect of existing vaccines against serogroup B meningococci, based on outer membrane proteins, is limited by strain restriction and apparent short duration of immune responses. In contrast, meningococcal colonization is known to stimulate the production of cross-protective antibodies as defined by the development of serum bactericidal activity (SBA) against heterologous serogroup B strains. In the current study, a resource of human serum samples and meningococcal carriage strains from studies of longitudinal carriage has been subjected to immunoproteomic analysis to investigate the outer membrane protein antigens associated with the development of SBA to both homologous and heterologous meningococcal serogroup B strains. Proteins from outer membranes of homologous and heterologous strains were separated by two-dimensional electrophoresis and reacted with paired sera which showed an increase in SBA following colonization. Individuals showed differing patterns of reactivity upon colonization, with an increase in SBA being associated with increases in the number of spots detected before and after colonization and/or with increases in the intensity of individual spots. Analysis of immunoreactive spots by mass spectrometry resulted in the identification of 43 proteins potentially associated with the development of SBA against both homologous and heterologous strains. The list of protein immunogens generated included not only well-established antigens but also novel proteins that represent potentially new candidates for inclusion in defined, multicomponent serogroup B vaccines.
* Corresponding author. Mailing address: Molecular Microbiology Group, Division of Infection, Inflammation and Immunity, University of Southampton Medical School, Mailpoint 814, Southampton General Hospital, Southampton SO16 6YD, United Kingdom. Phone: 44 2380 796974. Fax: 44 2380 796992. E-mail: jeh{at}soton.ac.uk
Published ahead of print on 8 September 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Infection and Immunity, November 2009, p. 5080-5089, Vol. 77, No. 11
0019-9567/09/$08.00+0 doi:10.1128/IAI.00701-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»