The Clinical Core Unit will provide support for three projects: Project 2 - Genetic variations in the innate immune response to Neisseria gononhoeae;Project 4 -The Altemative Complement Pathway (ACP) and Properdin in N. gonorrhoeae infection and Project 5 - Experimental and human protective immunity to N. gononhoeae infecfion. The core will recruit eligible subjects, collect and process serum specimens and cervico/lavage specimens from women and perfomn selected laboratory tests. The Clinical Core will: 1. Identify and enroll male subjects infected with N. gononhoeae and their female spread contacts. 2. Collect epidemiologic, clinical and laboratory data on female spread contacts at the Nanjing STD Clinic. 3. Collect, process and store gonococcal strains, blood and genital secrefions from women who are the sexpartners of a man wifii gonorrhea. 4. Perfonn PCR analysis for M. genitalium and 7. vaginalis and evaluate Gram's stains of vaginal secretions for BV (Nugent's criteria) to assess eligibility of female spread contacts to partidpate in a study of the role of naturally present vaccine antitrady (and blocking anfibody) in the acquisition of gonontiea. 5. Perform porin genotyping on gonococcal strains to validate transmission of like portypes between dually infected partners (Project 5). 6. Measure anfibody levels in blood, directed against candidate vaccine anfigens (2-1-L8 and 207 epitopes) and against the target (Rmp) of blocking antibodies in uninfected female spread contacts (Project 5). 7. Provide gonococcal strains and cervico/vaginal lavage specirr^ns from gononrhea infected female spread contacts (and uninfected contacts) to Project 2 for assessment of lipid A variations in sbains and for assessment of corresponding cytokine profiles in lavage specimens. 8. Provide cervico/vaginal lavage specimens to Project 4 to assess potential for ACP activation and the role of Properdin.

Public Health Relevance

Gonorrhea is a common sexually transmitted infection woridwide. Women may have few or no symptoms, which Often leads to delays in treatment and the development of complications: pelvic inflammatory disease, infertility and increased likelihood of acquiring HIV infecfion. Understanding innate and adapfive immune responses to gonorrtiea will lead to treatments and vaccines to lessen complicafions and prevent infecfion

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI084048-04
Application #
8381178
Study Section
Special Emphasis Panel (ZAI1-MMT-M)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$151,431
Indirect Cost
$32,655
Name
University of Massachusetts Medical School Worcester
Department
Type
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Shaughnessy, Jutamas; Gulati, Sunita; Agarwal, Sarika et al. (2016) A Novel Factor H-Fc Chimeric Immunotherapeutic Molecule against Neisseria gonorrhoeae. J Immunol 196:1732-40
Nudel, Kathleen; Massari, Paola; Genco, Caroline A (2015) Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2. Infect Immun 83:3410-7
Ayehunie, Seyoum; Islam, Ayesha; Cannon, Chris et al. (2015) Characterization of a Hormone-Responsive Organotypic Human Vaginal Tissue Model: Morphologic and Immunologic Effects. Reprod Sci 22:980-90
Gulati, Sunita; Mu, Xin; Zheng, Bo et al. (2015) Antibody to reduction modifiable protein increases the bacterial burden and the duration of gonococcal infection in a mouse model. J Infect Dis 212:311-5
Lewis, Lisa A; Gulati, Sunita; Burrowes, Elizabeth et al. (2015) α-2,3-sialyltransferase expression level impacts the kinetics of lipooligosaccharide sialylation, complement resistance, and the ability of Neisseria gonorrhoeae to colonize the murine genital tract. MBio 6:
McClure, Ryan; Nudel, Kathleen; Massari, Paola et al. (2015) The Gonococcal Transcriptome during Infection of the Lower Genital Tract in Women. PLoS One 10:e0133982
Su, Xiao-Hong; Wang, Bao-Xi; Le, Wen-Jing et al. (2015) Multidrug-Resistant Neisseria gonorrhoeae Isolates from Nanjing, China, Are Sensitive to Killing by a Novel DNA Gyrase Inhibitor, ETX0914 (AZD0914). Antimicrob Agents Chemother 60:621-3
Mavrogiorgos, Nikolaos; Mekasha, Samrawit; Yang, Yibin et al. (2014) Activation of NOD receptors by Neisseria gonorrhoeae modulates the innate immune response. Innate Immun 20:377-89
Agarwal, Sarika; Vasudhev, Shreekant; DeOliveira, Rosane B et al. (2014) Inhibition of the classical pathway of complement by meningococcal capsular polysaccharides. J Immunol 193:1855-63
Li, Sai; Su, Xiao-Hong; Le, Wen-Jing et al. (2014) Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from symptomatic men attending the Nanjing sexually transmitted diseases clinic (2011-2012): genetic characteristics of isolates with reduced sensitivity to ceftriaxone. BMC Infect Dis 14:622

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