Genetic Diversity and Carriage Dynamics ofNeisseria lactamicain Infants

Abstract

Neisseria lactamica, a harmless human commensal found predominantly in the upper respiratory tracts of infants, is closely related to Neisseria meningitidis, a pathogen of global significance. Colonization with N. lactamica may be responsible for the increase in immunity to meningococcal disease that occurs during childhood, when rates of meningococcal carriage are low. This observation has led to the suggestion that N. lactamica whole cells or components are potential constituents of novel meningococcal vaccines. However, the dynamics of carriage and population diversity of N. lactamica in children are poorly understood, presenting difficulties for the choice of representative isolates for use in vaccine development. This problem was addressed by the multilocus sequence typing of N. lactamica isolates from two longitudinal studies of bacterial carriage in infants. The studies comprised 100 and 216 subjects, with N. lactamica carriage monitored from age 4 weeks until age 96 weeks and from age 2 weeks until age 24 weeks, respectively. The maximum observed carriage rate was 44% at 56 weeks of age, with isolates obtained on multiple visits for the majority (54 of 75, 72%) of carriers. The N. lactamica isolates were genetically diverse, with 69 distinct genotypes recovered from the 75 infants. Carriage was generally long-lived, with an average rate of loss of under 1% per week during the 28 weeks following acquisition. Only 11 of the 75 infants carried more than one genotypically unique isolate during the course of the study. Some participants shared identical isolates with siblings, but none shared identical isolates with their parents. These findings have implications for the design of vaccines based on this organism.

Non-pathogenic Neisseria: members of an abundant, multi-habitat, diverse genus

“…The carriage rate peaks (w20 %) between 1-2 years after birth and thereafter declines with age to a low level (v5 %) in children of 14-17 years old. This is in sharp contrast to the carriage dynamics of N. meningitidis, which increases from birth and peaks in 15-to 19-year-olds, and then drops with age (Bennett et al, 2005;Cartwright et al, 1987;Gold et al, 1978). These observations led to the hypothesis that carriage of N. lactamica facilitates the development of natural immunity against meningococcus (Gold et al, 1978) and this has been exploited for the design of vaccines comprising N. lactamica-derived antigens, e.g.…”

“…The commensal Neisseria lactamica, in particular, has received significant attention for its potential to protect against N. meningitidis either through natural immunity (from carriage) (Evans et al, 2011) or by informing vaccine design. N. lactamica is a lactose-fermenting human commensal that is closely related to N. meningitidis (Bennett et al, 2005;Hollis et al, 1969). Colonization of the upper respiratory tract by this species starts soon after infants are born.…”

Absence of Mucosal Immunity in the Human Upper Respiratory Tract to the Commensal Bacteria Neisseria lactamica but Not Pathogenic Neisseria meningitidis during the Peak Age of Nasopharyngeal Carriage

“…The failure to detect T cell memory to Nl in early childhood was surprising because this is the period in which asymptomatic nasopharyngeal carriage of this organism is most frequent (17,18,22). It is possible that memory T cells from young children are less responsive to antigenic stimulation in vitro than cells from older children, or that there may be an increased rate of reversion from a cell surface CD45RO ϩ to CD45RA ϩ phenotype, as has been shown previously (34,35).…”

“…We have demonstrated the presence of memory T cell responses to Nm outer membrane vesicles (OMV) in human palatine tonsils (PT) which increase with age (16). However, although colonization by Nm induces a rapid immune response that protects against invasive disease, carriage studies have shown that single strains may colonize for several months before being cleared (17,18). It is unclear how Nm can colonize for prolonged periods of time while priming adaptive immunity without inducing an aberrant inflammatory response and associated immunopathology.…”

“…Colonization by Nl peaks at ϳ18 mo of age, before colonization by Nm (17,18,22), with Ͼ40% of infants becoming carriers in the first year of life (17). Like Nm, single isolates of Nl typically colonize the nasopharynx for several months (17,18) but the development of cellular immunity to this organism has not been studied.…”