Young women are highly vulnerable to HIV infection, particularly in endemic areas, with young adults making up 30-40% of new HIV infections globally. However, there is very little understanding of why there is discordant HIV infection susceptibility in adolescents versus adults. Furthermore, there is currently no established pre- clinical model to assess any prevention or therapeutic interventions with consideration of age. Here we aim to create the first nonhuman primate model of SIV infection and susceptibility in adolescents. We will assess the mucosal environment of the female genital tract (FGT) of adult compared to adolescent pigtail macaques (Macaca nemestrina). We will determine whether there are baseline differences across the menstrual cycle in adolescent versus adults, and will also determine whether adolescent pigtail macaques are more susceptible to SIV challenge. We will use state-of the art proteomic, microbiome, immunological and in vivo imaging techniques to take advantage of the in depth sampling (multiple tissue and longitudinal) capabilities of the nonhuman primate model. We will determine whether signatures associated with SIV/HIV susceptibility exist in adolescents compared to adults. We will also validate these studies using human cervicovaginal samples from adolescent and adult women. Furthermore, we will assess the mechanisms underlying an altered mucosal environment in adolescents. This will provide the first pre-clinical macaque model of HIV infection in adolescents that can delineate infection susceptibility, correlates of infection, and potential mechanisms underlying altered female genital tract in adolescents. These studies will be a critical advance in understanding of the increased susceptibility of adolescents to HIV infection, and provide the first model for testing interventions in young adults.

Public Health Relevance

Here we aim to create the first NHP model of SIV infection and susceptibility in adolescents. We will use this model to comprehensively assess both signatures and mechanisms associated with altered susceptibility in adolescents, and comparing these to young women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI128782-06
Application #
10220510
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Turpin, Jim A
Project Start
2020-07-22
Project End
2020-12-31
Budget Start
2020-07-22
Budget End
2020-12-31
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455