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Neisseria lactamica controlled human infection model

Neisseria lactamica controlled human infection model
Neisseria lactamica controlled human infection model

Neisseria lactamica is a nonpathogenic commensal of the human upper respiratory tract that has been associated with protection against N. meningitidis colonization and disease. We have previously utilized the N. lactamica controlled human infection model to investigate the protective effect of N. lactamica colonization on N. meningitidis colonization, the nature of cross-reactive immune responses mounted toward N. meningitidis following N. lactamica colonization, and the microevolution of N. lactamica over a 5-month colonization period. More recently, we have assessed the possibility of utilizing genetically modified strains of N. lactamica to enable use of the commensal as a vehicle for prolonged exposure of the nasopharynx of humans to antigens of interest, expressed in carried organisms. A controlled infection with N. lactamica expressing the meningococcal antigen NadA has been executed and the results demonstrate that this strategy is effective at generating immune responses to the target antigen. Throughout this chapter, we outline in a step-by-step manner the methodologies utilized when performing controlled human infection with N. lactamica including procedures relating to: (1) the dilution of N. lactamica stock vials to derive intranasal inocula, (2) the delivery of intranasal inocula to human volunteers, (3) the determination of N. lactamica colonization status following intranasal inoculation using oropharyngeal swabbing and nasal wash sampling, (4) the microbiological procedures utilized to identify N. lactamica colonization among study volunteers, and (5) the identification of N. lactamica colonies as strain Y92-1009 using polymerase chain reaction.

CHIME, Controlled human infection model, Human challenge, Neisseria lactamica, Neisseria meningitidis
1064-3745
387-404
Humana Press Inc.
Dale, Adam P
5663f3a5-e54c-40d5-a20f-dd93d2d64c56
Gbesemete, Diane F
2543380e-16b0-42b4-9d0f-88421ac33106
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Laver, Jay R
b2996398-2ccf-40f0-92b8-f338f3de796b
Bidmos, Fadil
Bossé, Janine
Langford, Paul
Dale, Adam P
5663f3a5-e54c-40d5-a20f-dd93d2d64c56
Gbesemete, Diane F
2543380e-16b0-42b4-9d0f-88421ac33106
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Laver, Jay R
b2996398-2ccf-40f0-92b8-f338f3de796b
Bidmos, Fadil
Bossé, Janine
Langford, Paul

Dale, Adam P, Gbesemete, Diane F, Read, Robert C and Laver, Jay R (2022) Neisseria lactamica controlled human infection model. In, Bidmos, Fadil, Bossé, Janine and Langford, Paul (eds.) Bacterial Vaccines: Methods and Protocols. (Methods in Molecular Biology, 2414) Humana Press Inc., pp. 387-404. (doi:10.1007/978-1-0716-1900-1_21).

Record type: Book Section

Abstract

Neisseria lactamica is a nonpathogenic commensal of the human upper respiratory tract that has been associated with protection against N. meningitidis colonization and disease. We have previously utilized the N. lactamica controlled human infection model to investigate the protective effect of N. lactamica colonization on N. meningitidis colonization, the nature of cross-reactive immune responses mounted toward N. meningitidis following N. lactamica colonization, and the microevolution of N. lactamica over a 5-month colonization period. More recently, we have assessed the possibility of utilizing genetically modified strains of N. lactamica to enable use of the commensal as a vehicle for prolonged exposure of the nasopharynx of humans to antigens of interest, expressed in carried organisms. A controlled infection with N. lactamica expressing the meningococcal antigen NadA has been executed and the results demonstrate that this strategy is effective at generating immune responses to the target antigen. Throughout this chapter, we outline in a step-by-step manner the methodologies utilized when performing controlled human infection with N. lactamica including procedures relating to: (1) the dilution of N. lactamica stock vials to derive intranasal inocula, (2) the delivery of intranasal inocula to human volunteers, (3) the determination of N. lactamica colonization status following intranasal inoculation using oropharyngeal swabbing and nasal wash sampling, (4) the microbiological procedures utilized to identify N. lactamica colonization among study volunteers, and (5) the identification of N. lactamica colonies as strain Y92-1009 using polymerase chain reaction.

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N._lactamica_controlled_human_infection_model._Dale_et_al_13.11.20 - Accepted Manuscript
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e-pub ahead of print date: 17 November 2021
Published date: November 2022
Additional Information: © 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: CHIME, Controlled human infection model, Human challenge, Neisseria lactamica, Neisseria meningitidis

Identifiers

Local EPrints ID: 453813
URI: http://eprints.soton.ac.uk/id/eprint/453813
ISSN: 1064-3745
PURE UUID: c72e87b0-1247-4167-8533-d67a85c61d95
ORCID for Robert C Read: ORCID iD orcid.org/0000-0002-4297-6728
ORCID for Jay R Laver: ORCID iD orcid.org/0000-0003-3314-5989

Catalogue record

Date deposited: 24 Jan 2022 17:54
Last modified: 17 Nov 2022 05:01

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Contributors

Author: Adam P Dale
Author: Diane F Gbesemete
Author: Robert C Read ORCID iD
Author: Jay R Laver ORCID iD
Editor: Fadil Bidmos
Editor: Janine Bossé
Editor: Paul Langford

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