Research ArticleVaccines

A recombinant commensal bacteria elicits heterologous antigen-specific immune responses during pharyngeal carriage

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Science Translational Medicine  07 Jul 2021:
Vol. 13, Issue 601, eabe8573
DOI: 10.1126/scitranslmed.abe8573

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A commensal vaccine

Neisseria lactamica (Nlac) is a commensal bacteria that is found in the upper respiratory tract of infants and young children and has been shown to safely colonize the nasopharynx of adults after experimental infection. Thus, Nlac has the capacity to serve as a live vaccine vector against other mucosal pathogens. To test this, Laver et al. used a controlled human infection study to demonstrate that colonization with Nlac expressing a protein derived from Neisseria meningitidis (Nmen) elicited immune responses against the Nmen protein in volunteers, which was characterized by both antibody and memory B cell responses. Further, the controlled infection was safe and did not result in transmission to volunteers’ contacts. In summary, Nlac may be an effective and safe vaccine vector in humans.


The human nasopharynx contains a stable microbial ecosystem of commensal and potentially pathogenic bacteria, which can elicit protective primary and secondary immune responses. Experimental intranasal infection of human adults with the commensal Neisseria lactamica produced safe, sustained pharyngeal colonization. This has potential utility as a vehicle for sustained release of antigen to the human mucosa, but commensals in general are thought to be immunologically tolerated. Here, we show that engineered N. lactamica, chromosomally transformed to express a heterologous vaccine antigen, safely induces systemic, antigen-specific immune responses during carriage in humans. When the N. lactamica expressing the meningococcal antigen Neisseria Adhesin A (NadA) was inoculated intranasally into human volunteers, all colonized participants carried the bacteria asymptomatically for at least 28 days, with most (86%) still carrying the bacteria at 90 days. Compared to an otherwise isogenic but phenotypically wild-type strain, colonization with NadA-expressing N. lactamica generated NadA-specific immunoglobulin G (IgG)– and IgA-secreting plasma cells within 14 days of colonization and NadA-specific IgG memory B cells within 28 days of colonization. NadA-specific IgG memory B cells were detected in peripheral blood of colonized participants for at least 90 days. Over the same period, there was seroconversion against NadA and generation of serum bactericidal antibody activity against a NadA-expressing meningococcus. The controlled infection was safe, and there was no transmission to adult bedroom sharers during the 90-day period. Genetically modified N. lactamica could therefore be used to generate beneficial immune responses to heterologous antigens during sustained pharyngeal carriage.

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