Three-quarters of men and one-quarter of women who are exposed to a partner infected with Neisseria gonorrhoae do not become infected. Resistance to experimental infection in men is correlated with the presence of serum IgG antibodies directed against Paraglobosyl lipooligosaccharides (LOS);4-5% of male soldiers develop these antibodies during natural infection. In a study of STD Clinic clientele, we found that serum concentrations of Paraglobosyl LOS IgG were higher in those who had had prior gonococcal infections than in those who had not. There was a threshold of LOS IgG above which no clients reported to the STO Clinics with active gonococcal infections, either at the time the sera were drawn or over several years of follow-up. This threshold was present in 10-15% of individuals in the Baltimore core mixing population. The risk of exposure experienced by the clients during follow up was not known. In order to test the hypothesis that Paraglobosyl LOS IgG contributes to resistance to gonococcal infection, we need to determine serum Paraglobosyl IgG concentrations at or near the time of exposure. We propose recruiting the partners of STD clients with active gonococcal infections as soon as they are identified. We will measure concentrations of Paraglogosyl LOS IgG in the serum and cervical secretions (women) of partners and determine whether they are infected. We will find out whether concentrations of serum or local LOS IgG are higher in contacts of patients who resist infection than in those who do not. We will use RT-PCR of polyG tracts of gonococci in Gram stained exudates to find out which LOS molecules are present during transmission. We will compare local and systemic LOS IgG among symptomatic and asymptomatic, but infected, patients and contacts. Two other variables may confound the interpretation of data in women: whether their genital epithelial cells constitutively express CEACAM and whether their vaginal flora include lactobaccilli that produce H2O2. Ligation of CEACAM by gonococci leads to bacterial death, in vitro. Only ca. 30% of women constitutively express CEACAM;constitutive CEACAM expression may lower the risk of acquiring infection following exposure. We will compare constitutive CEACAM expression and lactobacilli colonization among women who do and do not become infected after exposure. We will use bacterial vaginosis as a surrogate for the absence of H2O2-expressing lactobacilli. The results of these studies will expand our understanding of resistance to gonococcal infection and may provide the basis for the development of a Paraglobosyl LOS vaccine that, if sufficiently immunogenic, could prevent gonococcal transmission among those at highest risk for infection.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
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Hiltke, Thomas J
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Northern California Institute Research & Education
San Francisco
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John, Constance M; Liu, Mingfeng; Phillips, Nancy J et al. (2012) Lack of lipid A pyrophosphorylation and functional lptA reduces inflammation by Neisseria commensals. Infect Immun 80:4014-26
McLaughlin, Stephanie E; Cheng, Hui; Ghanem, Khalil G et al. (2012) Urethral exudates of men with Neisseria gonorrhoeae infections select a restricted lipooligosaccharide phenotype during transmission. J Infect Dis 206:1227-32
Brotman, R M; Melendez, J H; Ghanem, K G (2011) A case control study of anovaginal distance and bacterial vaginosis. Int J STD AIDS 22:231-3
Swanson, Karen V; Griffiss, J McLeod; Edwards, Vonetta L et al. (2011) Neisseria gonorrhoeae-induced transactivation of EGFR enhances gonococcal invasion. Cell Microbiol 13:1078-90
Cheng, Hui; Yang, Zhijie; Estabrook, Michele M et al. (2011) Human lipooligosaccharide IGG that prevents endemic meningococcal disease recognizes an internal lacto-N-neotetraose structure. J Biol Chem 286:43622-33
O'Connor, Ellen T; Zhou, Hui; Bullock, Kevin et al. (2009) Structural characterization of an oligosaccharide made by Neisseria sicca. J Bacteriol 191:3311-20
O'Connor, Ellen T; Swanson, Karen V; Cheng, Hui et al. (2008) Structural requirements for monoclonal antibody 2-1-L8 recognition of neisserial lipooligosaccharides. Hybridoma (Larchmt) 27:71-9