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Immunoproteomic analysis of the development of natural immunity in subjects colonized by Neisseria mengitidis reveals potential vaccine candidates

Immunoproteomic analysis of the development of natural immunity in subjects colonized by Neisseria mengitidis reveals potential vaccine candidates
Immunoproteomic analysis of the development of natural immunity in subjects colonized by Neisseria mengitidis reveals potential vaccine candidates
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
0019-9567
5080-5089
Williams, Jeanette N.
b8cee39f-8709-40ac-84ad-e62e3c1c7d8e
Skipp, Paul J.
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
O'connor, David
7c29ec66-081e-46f0-8be8-bac6a7dc8de8
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Williams, Jeanette N.
b8cee39f-8709-40ac-84ad-e62e3c1c7d8e
Skipp, Paul J.
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
O'connor, David
7c29ec66-081e-46f0-8be8-bac6a7dc8de8
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31

Williams, Jeanette N., Skipp, Paul J., O'connor, David, Christodoulides, Myron and Heckels, John E. (2009) Immunoproteomic analysis of the development of natural immunity in subjects colonized by Neisseria mengitidis reveals potential vaccine candidates. Infection and Immunity, 77 (11), 5080-5089. (doi:10.1128/IAI.00701-09).

Record type: Article

Abstract

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

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More information

Published date: November 2009
Organisations: Infection Inflammation & Immunity, Biological Sciences

Identifiers

Local EPrints ID: 72736
URI: http://eprints.soton.ac.uk/id/eprint/72736
ISSN: 0019-9567
PURE UUID: 6e0ebae9-9f32-45b1-82da-fdde32993d26
ORCID for Paul J. Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for Myron Christodoulides: ORCID iD orcid.org/0000-0002-9663-4731

Catalogue record

Date deposited: 22 Feb 2010
Last modified: 14 Mar 2024 02:35

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Contributors

Author: Jeanette N. Williams
Author: Paul J. Skipp ORCID iD
Author: David O'connor
Author: John E. Heckels

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