The human mucosal immune response to Neisseria meningitidis.

Research archive

Natural vaccination through colonisation by the meningococcus or by related organisms such as N. lactamica is thought to result in protective immunity. However, the mechanisms of this host defence, particularly at the mucosal level, are poorly defined. In a pilot study funded by the Foundation we have established the immunological assays necessary to investigate the naturally acquired mucosal T-cell response to meningococcal subcapsular protein antigens. Using human tonsils, we have defined the cellular profile of the tissues under study, and have generated preliminary data describing the kinetics and specificity of the T-cell responses elicited. This novel approach has provided a potential window into the mechanisms of immunity at the mucosal level. We propose to exploit our findings and expertise to address three specific aims:

(a) To determine whether T-cell mediated immunological memory to meningococcal antigens is located at the mucosal level;
(b) To define the immunoregulatory nature of the observed mucosal T-cell immune responses; and
(c) To relate the nature of this regulatory mucosal T-cell response to the presence of systemic immunity.

This will enable us to determine whether immunosurveillance by T-cells at the mucosal surface is potentially boostable by either colonisation or vaccination and explore the possibility that colonisation by pathogenic and non-pathogenic Neisseria induces immunological tolerance. Understanding naturally acquired mucosal immunity to the meningococcus will better inform the development and implementation of new vaccine strategies with the potential to prevent disease and impact on meningococcal colonisation.

Read our news release on this project:

Bristol scientists in meningitis vaccine bid

Results from this study have been published in scientific journals as follows:

Davenport V, Guthrie T, Findlow J, Borrow R, Williams NA, Heyderman RS.
Evidence for naturally acquired T cell-mediated mucosal immunity to Neisseria meningitidis.
J Immunol 2003 Oct 15;171(8):4263-70.
http://www.jimmunol.org/cgi/reprint/171/8/4263.pdf

Horton RE, Stuart J, Christensen H, Borrow R, Guthrie T, Davenport V, Finn A, Williams NA, Heyderman RS.
Influence of age and carriage status on salivary IgA to Neisseria meningitidis.
Epidemiol Infect 2005 Oct;133(5):883-9.
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=299720

Guthrie T, Hobbs CG, Davenport V, Horton RE, Heyderman RS, Williams NA.
Parenteral influenza vaccination influences mucosal and systemic T cell-mediated immunity in healthy adults.
J Infect Dis 2004 Dec 1;190(11):1927-35. Epub 2004 Oct 27.
http://www.journals.uchicago.edu/JID/journal/issues/v190n11/32527/32527.web.pdf

Davenport V, Groves E, Hobbs CC, Williams NA, Heyderman RS. Regulation of Th-1 T cell-dominated immunity to Neisseria meningitidis within the human mucosa
Cell Microbiol 2006 Dec 12; [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17166235&query_hl=49&itool=pubmed_docsum

Heyderman RS, Davenport V, Williams NA.
Mucosal immunity and optimizing protection with meningococcal serogroup B vaccines.
Trends Microbiol. 2006 Mar;14(3):120-4. Epub 2006 Feb 15.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16469496&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum