A novel, multi-compartment intravaginal ring for prevention of genital herpes and unintended pregnancy

Active Project Grant Awarded Last action

Award ID
R01AI175437
Recipient
Awarding agency
Obligated
$2,485,541

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 43% complete
Place of performance
Monrovia, CA 91016, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Genital herpes simplex virus (HSV) infection is one of the most common sexually transmitted infections worldwide. The infection is lifelong: there currently is no cure and no vaccine. In addition, HSV-1 and -2, human papillomavirus (HPV), and human immunodeficiency virus (HIV) are responsible for intersecting epidemics, where the disease caused by one virus facilitates the transmission and/or pathogenesis of the other. Numerous studies suggest that user-controlled multipurpose products providing HSV prevention -ideally along with HPV and HIV- in combination with contraception would strongly motivate higher uptake relative to single-purpose products: women not self-identifying as at risk of HSV infection would use a multipurpose product to avoid pregnancy, resulting in significantly improved user compliance, and hence effectiveness, relative to single-purpose antiviral products. Many women would prefer a topical (vaginal) nonhormonal contraception method that, unlike vaginal gels, does not require use immediately before or after SEX. Our application integrates key innovations in developing a next generation multipurpose technology (MPT) intravaginal ring (IVR) comprised of: (1) antiviral peptide lead candidate with activity against HSV, HPV, and HIV; (2) small-molecule inhibitors of sperm functions required to reach and fertilize the oocyte; and (3) a novel IVR platform for long-acting, controlled delivery of the two-drug combination. We have designed and synthesized a library of small antiviral peptides that disrupt a range of viruses, including HSV, HPV, and HIV, at low ΜM concentrations. An existing lead candidate, optimized for vaginal delivery, has been selected for IVR formulation under the current application. In parallel, we have designed and synthesized a library of highly potent, small-molecule inhibitors of soluble adenylyl cyclase (SAC) that effectively block sperm motility and prevent in vitro fertilization at sub NM concentrations. Finally, our team developed an innovative IVR platform for the delivery of drug combinations, including small molecules and biomolecules, at independently controlled rates. In aim 1, we will evaluate our panel of SAC inhibitor late-lead candidates using biochemical, functional, and pharmacological assays to select a lead candidate designed specifically for vaginal dosing. In aim 2, we will formulate and evaluate in vitro human-sized MPT ivrs to deliver our lead antiviral peptide and lead contraceptive combinations at target in vitro rates. In aim 3, we will assess the pharmacokinetics and pharmacodynamics (safety and anti-HSV efficacy) of MPT IVR candidates in mice (efficacy and preliminary safety) and sheep (pharmacokinetics and safety). This project builds on an established collaboration of investigators and will advance our scientific knowledge on vaginal delivery of novel agents in the context of HSV prevention and nonhormonal contraception.

Transactions

Action Obligated Date
Amendment $815,431
Amendment $828,713
Amendment $81,534
Original award $759,863

Subawards

Subrecipient Amount Awarded
University Of Texas Medical Branch At Galveston Perform studies in sheep for assessment of safety and pharmacokinetics of drug for HIV prevention delivered via a subcutaneous implant. $44,669
Weill Medical College Of Cornell University Use functional and pharmacological assays to select the sAC inhibitors most suitable for delivery via an multiprotection technology intravaginal ring (IVR). $898,350
Scripps Research Institute Screening peptides for their abilities to neutralize in vitro HIV-1, HSV and HPV in the absence of cellular toxicities. $381,622

Quick answers

Who received award R01AI175437?

R01AI175437 was awarded to Oak Crest Institute Of Science by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on September 10, 2024.

How much is award R01AI175437 worth?

$2,485,541 has been obligated on R01AI175437.

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