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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References
Laver JR, Hughes SE, Read RC (2015) Neisserial molecular adaptations to the nasopharyngeal niche. Adv Microb Physiol 66:323–355
Christensen H, May M, Bowen L et al (2010) Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis 10:853–861
Maiden MCJ, Ibarz-Pavón AB, Urwin R et al (2008) Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity. J Infect Dis 197:737–743
Gold R, Goldschneider I, Lepow ML et al (1978) Carriage of Neisseria meningitidis and Neisseria lactamica in infants and children. J Infect Dis 137:112–121
Cartwright KA, Stuart JM, Jones DM et al (1987) The stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica. Epidemiol Infect 99:591–601
Coen PG, Cartwright K, Stuart J (2000) Mathematical modeling of infection and disease due to Neisseria meningitidis and Neisseria lactamica. Int J Epidemiol 29:180–188
Gorringe AR, Taylor S, Brookes C et al (2009) Phase I safety and immunogenicity study of a candidate meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles. Clin Vaccine Immunol 16:1113–1120
Evans CM, Pratt CB, Matheson M et al (2011) Nasopharyngeal colonization by Neisseria lactamica and induction of protective immunity against Neisseria meningitidis. Clin Infect Dis 52:70–77
Deasy AM, Guccione E, Dale AP et al (2015) Nasal inoculation of the commensal Neisseria lactamica inhibits carriage of Neisseria meningitidis by young adults: a controlled human infection study. Clin Infect Dis 60:1512–1520
Pandey AK, Cleary DW, Laver JR et al (2017) Neisseria lactamica Y92-1009 complete genome sequence. Stand Genomic Sci 12:41
Pandey AK, Cleary DW, Laver JR et al (2018) Microevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection. Nat Commun 9:4753
Dale AP, Theodosiou AA, Laver JR et al (2020) Controlled human infection with Neisseria lactamica induces B-cell responses that are cross-reactive with Neisseria meningitidis. J Immunol 204:231.21
Gbesemete D, Laver JR, de Graaf H et al (2019) Protocol for a controlled human infection with genetically modified Neisseria lactamica expressing the meningococcal vaccine antigen NadA: a potent new technique for experimental medicine. BMJ Open 9:e026544
Laver JR, Gbesemete D, Dale AP et al (2021) A recombinant commensal bacteria elicits heterologous antigen-specific immune responses during pharyngeal carriage. Sci Transl Med 13:eabe8573
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Dale, A.P., Gbesemete, D.F., Read, R.C., Laver, J.R. (2022). Neisseria lactamica Controlled Human Infection Model. In: Bidmos, F., Bossé, J., Langford, P. (eds) Bacterial Vaccines. Methods in Molecular Biology, vol 2414. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1900-1_21
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DOI: https://doi.org/10.1007/978-1-0716-1900-1_21
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