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
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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) ?-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:
Lewis, Lisa A; Ram, Sanjay (2014) Meningococcal disease and the complement system. Virulence 5:98-126

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