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Next Generation Multipurpose Prevention Technology: An Intravaginal Ring for HIV Prevention and Nonhormonal Contraception

Award Number: R01HD101344
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT New HIV infection rates far outpace the targets set by global health organizations, despite important progress in curbing the progression of the epidemic. In 2017, an estimated 1.8 million people became newly HIV infected globally. New HIV pre-exposure prophylaxis (PrEP) strategies are needed urgently to curb this alarming situation, particularly in young sub-Saharan African women who are disproportionately at risk. A high proportion of women at risk of becoming HIV-infected also are interested in family planning, suggesting that a dual-purpose product providing HIV prevention and contraception would significantly increase the likelihood of higher uptake relative to single-purpose products, since unsurprisingly, women do not self-identify as being at risk of HIV, but do so identify for pregnancy. Many women are averse to exogenous hormones and would strongly prefer a nonhormonal method, and one that does not require use immediately before or after sex. Our application integrates two leading innovations in developing a next generation multi-purpose technology (MPT) intravaginal ring (IVR): (1) developing a novel, nonhormonal contraceptive agent based on a multivalent monoclonal antibody (mAb) that blocks sperm from swimming through mucus and accessing the egg; and (2) formulating the mAb contraceptive with antiretroviral (ARV) agents with demonstrated clinical efficacy in preventing HIV in a behavior-monitoring IVR. We have recently engineered a unique IgG-based multivalent mAb with 10 Fab arms against CD52g, a validated antigen target for contraception that is found only on cells in the human male genital tract. This molecule, even at sub-nanomolar concentrations, effectively agglutinates >99% of sperm within seconds, thus offering potentially potent yet cost-effective contraception. To complement this novel agent, our team has developed an innovative IVR platform that delivers drug combinations including small molecule drugs and mAbs. A low-cost module has been incorporated into the IVR to monitor temperature as a surrogate measure of adherence. The MPT IVR will be formulated to provide long-term (30 days) dual protection while evaluating adherence. In Aim 1, we will further enhance the mAb constructs against CD52g through affinity maturation of anti-CD52g Fab using yeast-display, incorporate the optimized Fab into similar multimeric mAb formats, and characterize their sperm agglutination potencies rigorously. In Aim 2, we will formulate and evaluate in vitro human- and macaque-sized MPT IVRs to deliver our lead contraceptive mAb candidate in combination with ARV drugs at target in vitro rates based on existing in vivo PK-PD data. We will optimize and expand the adherence IVR design and evaluate prototypes in sheep. In Aim 3, we will assess the pharmacokinetics and pharmacodynamics (safety and efficacy) of MPT IVR candidates in sheep and pigtailed macaques. This project builds on an established collaboration of investigators and will advance our scientific knowledge on the properties of sustained-release vaginal drug delivery in the context of HIV prevention and contraception.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $655,765 )
2024	2024	OAK CREST INSTITUTE OF SCIENCE	132 W CHESTNUT AVE	MONROVIA	CA	91016	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	5	3/13/2024	NON-COMPETING CONTINUATION	$655,765
														Subtotal = $655,765

Issue Date FY: 2023 ( Subtotal = $746,693 )
2023	2023	OAK CREST INSTITUTE OF SCIENCE	132 W CHESTNUT AVE	MONROVIA	CA	91016	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	4	3/7/2023	NON-COMPETING CONTINUATION	$746,693
														Subtotal = $746,693

Issue Date FY: 2022 ( Subtotal = $740,660 )
2022	2022	OAK CREST INSTITUTE OF SCIENCE	132 W CHESTNUT AVE	MONROVIA	CA	91016	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	3	3/8/2022	NON-COMPETING CONTINUATION	$666,593
2022	2022	OAK CREST INSTITUTE OF SCIENCE	132 W CHESTNUT AVE	MONROVIA	CA	91016	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	3	4/25/2022	NON-COMPETING CONTINUATION	$74,067
														Subtotal = $740,660

Issue Date FY: 2021 ( Subtotal = $744,855 )
2021	2021	OAK CREST INSTITUTE OF SCIENCE	132 W CHESTNUT AVE	MONROVIA	CA	91016	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	2	8/27/2021	NON-COMPETING CONTINUATION	$14,897
2021	2021	OAK CREST INSTITUTE OF SCIENCE	132 W CHESTNUT AVE	MONROVIA	CA	91016	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	2	2/24/2021	NON-COMPETING CONTINUATION	$729,958
														Subtotal = $744,855

Issue Date FY: 2020 ( Subtotal = $759,199 )
2020	2020	OAK CREST INSTITUTE OF SCIENCE	132 W CHESTNUT AVE	MONROVIA	CA	91016	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	1	5/4/2020	NEW	$759,199
														Subtotal = $759,199

Grand Total All Awards = $3,647,172

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Next Generation Multipurpose Prevention Technology: An Intravaginal Ring for HIV Prevention and Nonhormonal Contraception

Award Number: R01HD101344

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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