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Nasopharyngeal colonization by neisseria lactamica and induction of protective immunity against neisseria meningitidis

Nasopharyngeal colonization by neisseria lactamica and induction of protective immunity against neisseria meningitidis
Nasopharyngeal colonization by neisseria lactamica and induction of protective immunity against neisseria meningitidis
Background: Natural immunity to Neisseria meningitidis may result from nasopharyngeal carriage of closely related commensals, such as Neisseria lactamica.

Methods: We enrolled 61 students with no current carriage of Neisseria species and inoculated them intranasally with 10,000 colony-forming units of Neisseria lactamica or sham control. Colonization was monitored in oropharyngeal samples over 6 months. We measured specific mucosal and systemic antibody responses to N. lactamica and serum bactericidal antibody (SBA) and opsonophagocytic antibodies to a panel of N. meningitidis serogroup B strains. We also inoculated an additional cohort following vaccination with N. lactamica outer-membrane vesicles (OMV) produced from the same strain.

Results: Twenty-six (63.4%) of 41 inoculated individuals became colonized with N. lactamica; 85% remained colonized at 12 weeks. Noncarriers were resistant to rechallenge, and carriers who terminated carriage were relatively resistant to rechallenge. No carriers acquired N. meningitidis carriage over 24 weeks, compared with 3 control subjects (15%). Carriers developed serum IgG and salivary IgA antibodies to the inoculated N. lactamica strain by 4 weeks; noncarriers and control subjects did not. Cross-reactive serum bactericidal antibody responses to N.meningitidis were negligible in carriers, but they developed broad opsonophagocytic antimeningococcal antibodies. OMV vaccinees developed systemic and mucosal anti–N. lactamica antibodies and were relatively resistant to N. lactamica carriage but not to natural acquisition of N. meningitidis.

Conclusions: Carriers of N. lactamica develop mucosal and systemic humoral immunity to N. lactamica together with cross-reacting systemic opsonophagocytic but not bactericidal antibodies to N. meningitidis. Possession of humoral immunity to N. lactamica inhibits acquisition of N. lactamica but not of N. meningitidis. Some individuals are intrinsically resistant to N. lactamica carriage, independent of humoral immunity.
1058-4838
70-77
Evans, C.M.
d530ec6a-92c3-4fef-8166-415c9d8a9021
Pratt, C.B.
3bb886d7-d11c-443d-ab23-b9fafd1a94bb
Matheson, M.
db824731-ab98-497f-9b82-203eefb75e14
Vaughan, T.E.
74ba2750-8ae1-4847-8e80-5054eb149a64
Findlow, J.
da01e864-610a-4320-a891-bdb1d0722bbe
Borrow, R.
ae200ab8-f9f3-49c6-a161-c8fc31d00a58
Gorringe, A.R.
f83c735c-864e-4e00-99b8-f4671e4a7f6c
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Evans, C.M.
d530ec6a-92c3-4fef-8166-415c9d8a9021
Pratt, C.B.
3bb886d7-d11c-443d-ab23-b9fafd1a94bb
Matheson, M.
db824731-ab98-497f-9b82-203eefb75e14
Vaughan, T.E.
74ba2750-8ae1-4847-8e80-5054eb149a64
Findlow, J.
da01e864-610a-4320-a891-bdb1d0722bbe
Borrow, R.
ae200ab8-f9f3-49c6-a161-c8fc31d00a58
Gorringe, A.R.
f83c735c-864e-4e00-99b8-f4671e4a7f6c
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Evans, C.M., Pratt, C.B., Matheson, M., Vaughan, T.E., Findlow, J., Borrow, R., Gorringe, A.R. and Read, R.C. (2011) Nasopharyngeal colonization by neisseria lactamica and induction of protective immunity against neisseria meningitidis. Clinical Infectious Diseases, 52 (1), 70-77. (doi:10.1093/cid/ciq065). (PMID:21148522)

Record type: Article

Abstract

Background: Natural immunity to Neisseria meningitidis may result from nasopharyngeal carriage of closely related commensals, such as Neisseria lactamica.

Methods: We enrolled 61 students with no current carriage of Neisseria species and inoculated them intranasally with 10,000 colony-forming units of Neisseria lactamica or sham control. Colonization was monitored in oropharyngeal samples over 6 months. We measured specific mucosal and systemic antibody responses to N. lactamica and serum bactericidal antibody (SBA) and opsonophagocytic antibodies to a panel of N. meningitidis serogroup B strains. We also inoculated an additional cohort following vaccination with N. lactamica outer-membrane vesicles (OMV) produced from the same strain.

Results: Twenty-six (63.4%) of 41 inoculated individuals became colonized with N. lactamica; 85% remained colonized at 12 weeks. Noncarriers were resistant to rechallenge, and carriers who terminated carriage were relatively resistant to rechallenge. No carriers acquired N. meningitidis carriage over 24 weeks, compared with 3 control subjects (15%). Carriers developed serum IgG and salivary IgA antibodies to the inoculated N. lactamica strain by 4 weeks; noncarriers and control subjects did not. Cross-reactive serum bactericidal antibody responses to N.meningitidis were negligible in carriers, but they developed broad opsonophagocytic antimeningococcal antibodies. OMV vaccinees developed systemic and mucosal anti–N. lactamica antibodies and were relatively resistant to N. lactamica carriage but not to natural acquisition of N. meningitidis.

Conclusions: Carriers of N. lactamica develop mucosal and systemic humoral immunity to N. lactamica together with cross-reacting systemic opsonophagocytic but not bactericidal antibodies to N. meningitidis. Possession of humoral immunity to N. lactamica inhibits acquisition of N. lactamica but not of N. meningitidis. Some individuals are intrinsically resistant to N. lactamica carriage, independent of humoral immunity.

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Published date: January 2011
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 341691
URI: http://eprints.soton.ac.uk/id/eprint/341691
ISSN: 1058-4838
PURE UUID: 35f45a96-de64-430d-93c8-b61ddb9a3edb
ORCID for R.C. Read: ORCID iD orcid.org/0000-0002-4297-6728

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Date deposited: 06 Aug 2012 10:26
Last modified: 15 Mar 2024 03:42

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Contributors

Author: C.M. Evans
Author: C.B. Pratt
Author: M. Matheson
Author: T.E. Vaughan
Author: J. Findlow
Author: R. Borrow
Author: A.R. Gorringe
Author: R.C. Read ORCID iD

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