Dynamics of Carriage of Neisseria meningitidis in a Group of Military Recruits: Subtype Stability and Specificity of the Immune Response following Colonization

Jones, Graeme R.; Christodoulides, Myron; Brooks, Joy L.; Miller, A. R. O.; Cartwright, Keith; Heckels, John E.

doi:10.1086/515622

Cited by 82 publications

(60 citation statements)

References 29 publications

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“…Homologous and heterologous antibodies to the other major OM porin PorB (spot 11) were also detected following colonization. The patterns of immunoreactivity to both porins observed in the current study support the results of previous studies that reported a correlation between bactericidal activity and an increase in antiporin antibodies in response to both meningococcal infection (17,58) and colonization (23,26). This result is also in accord with the observation that a subset of antibodies directed against PorA and PorB show heterologous as well as serosubtype specificity (58).…”

Section: Discussionsupporting

confidence: 92%

Immunoproteomic Analysis of the Development of Natural Immunity in Subjects Colonized by Neisseria meningitidis Reveals Potential Vaccine Candidates

et al. 2009

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The potential protective effect of existing vaccines against serogroup B meningococci, based on outer membrane proteins, is limited by strain restriction and apparent short duration of immune responses. In contrast, meningococcal colonization is known to stimulate the production of cross-protective antibodies as defined by the development of serum bactericidal activity (SBA) against heterologous serogroup B strains. In the current study, a resource of human serum samples and meningococcal carriage strains from studies of longitudinal carriage has been subjected to immunoproteomic analysis to investigate the outer membrane protein antigens associated with the development of SBA to both homologous and heterologous meningococcal serogroup B strains. Proteins from outer membranes of homologous and heterologous strains were separated by two-dimensional electrophoresis and reacted with paired sera which showed an increase in SBA following colonization. Individuals showed differing patterns of reactivity upon colonization, with an increase in SBA being associated with increases in the number of spots detected before and after colonization and/or with increases in the intensity of individual spots. Analysis of immunoreactive spots by mass spectrometry resulted in the identification of 43 proteins potentially associated with the development of SBA against both homologous and heterologous strains. The list of protein immunogens generated included not only well-established antigens but also novel proteins that represent potentially new candidates for inclusion in defined, multicomponent serogroup B vaccines.

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Section: Discussionsupporting

confidence: 92%

Immunoproteomic Analysis of the Development of Natural Immunity in Subjects Colonized by Neisseria meningitidis Reveals Potential Vaccine Candidates

et al. 2009

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“…Protective antibodies to N. meningitidis group C strains can be directed at a number of antigenic targets, including the capsular polysaccharide or noncapsular antigens, such as PorA (18) or Opc (class 5 outer membrane proteins) (31). Based on absorption studies of gamma globulin prepared from more than 2,000 North American donors, Goldschneider et al concluded that the majority of naturally acquired group C serum bactericidal activity was directed against the capsular polysaccharide (10), which is consistent with our absorption data on individual sera.…”

Section: Discussionmentioning

confidence: 99%

Naturally Acquired Passive Protective Activity against Neisseria meningitidis Group C in the Absence of Serum Bactericidal Activity

Welsch¹,

Granoff²

2004

Infect Immun

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The hallmark of immunity to meningococcal disease is a bactericidal titer in serum of >1:4 measured with human complement, but this threshold titer may underestimate the extent of protection. We used the infant rat model of meningococcal bacteremia to measure group C passive protective activity in serum samples from 91 unimmunized adults living in California. A total of 35 sera (38.5%) had passive protective activity. Sera with complement-mediated bactericidal titers of >1:4 were 3.4-fold more likely to confer protection (89%) than nonbactericidal sera (26%; P < 0.0001). Thus, bactericidal titers of >1:4 are a marker of protection, but this threshold lacks sensitivity for predicting protective activity. We investigated the 73 sera with bactericidal titers of <1:4 to determine the basis of protective activity. The 19 sera with protective activity had a higher geometric mean group C anticapsular antibody concentration (0.72 g/ml) than the 54 sera that lacked protective activity (0.16 g/ml; P < 0.001). Thus, protective activity in the absence of bactericidal activity was associated with higher concentrations of anticapsular antibodies, but not all sera with anticapsular antibodies conferred protection. Of 18 nonbactericidal sera with anticapsular antibody concentrations between 0.31 and 0.99 g/ml, the 11 sera that conferred protection had a higher mean antibody avidity constant (21.9 nM ؊1 ) than the 7 nonprotective sera (14.6 nM ؊1 ; P < 0.03). Thus, in sera with titers of <1:4, protective activity is associated with higher-avidity group C anticapsular antibodies, which are present in concentrations insufficient to elicit complement-mediated bacteriolysis in vitro but sufficient to confer protection in an in vivo bacteremia model.

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“…However, porA may be a more appropriate target than ctrA for PCR-based detection of meningococcal carriage. In addition, porA PCR would enable the determination of subcapsular antigens, which have been associated with the development of specific immunity (9).…”

Section: Discussionmentioning

confidence: 99%

Detection of Meningococcal Carriage by Culture and PCR of Throat Swabs and Mouth Gargles

et al. 2002

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The standard method for detecting meningococcal carriage is culture of throat swabs on selective media, but the levels of carriage determined depend heavily on the skills of the individuals taking the swab and interpreting the cultures. This study aimed to determine the most sensitive detection method for meningococcal carriage. Throat swabs and saline mouth gargles, obtained from 89 university students, were processed in parallel by conventional culture and TaqMan ctrA PCR. Carriage of meningococci, as detected by the combined methods, was 20%. The sensitivities of throat swab culture, throat swab PCR, gargle culture, and gargle PCR were 72, 56, 56, and 50%, respectively, and the probabilities that these techniques would correctly identify the absence of carriage (negative predictive value [NPV]) were 93.4, 89.9, 89.9, and 88.8%. Culturing both throat swabs and gargles increased the NPV to 98.6%. The further addition of throat swab PCR increased this to 100%. Testing gargles by both culture and PCR was as sensitive as testing throat swabs by both methods, suggesting that gargles may be a suitable alternative for large-scale screening studies when throat swabs are difficult to obtain, although they required more lengthy laboratory processing. PCR was a useful adjunct to culture for detecting nasopharyngeal carriage, but it failed to detect some nongroupable strains. For maximum sensitivity, a combination of techniques was required. This study indicates the confidence with which health care professionals involved in meningococcal screening can regard laboratory results.

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Dynamics of Carriage of Neisseria meningitidis in a Group of Military Recruits: Subtype Stability and Specificity of the Immune Response following Colonization

Cited by 82 publications

References 29 publications

Immunoproteomic Analysis of the Development of Natural Immunity in Subjects Colonized by Neisseria meningitidis Reveals Potential Vaccine Candidates

Immunoproteomic Analysis of the Development of Natural Immunity in Subjects Colonized by Neisseria meningitidis Reveals Potential Vaccine Candidates

Naturally Acquired Passive Protective Activity against Neisseria meningitidis Group C in the Absence of Serum Bactericidal Activity

Detection of Meningococcal Carriage by Culture and PCR of Throat Swabs and Mouth Gargles

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