Description:
Fast Track Proposals will be accepted.
Direct-to-Phase II will not be accepted.
Number of anticipated awards: 1-3
Budget (total costs):
Phase I: $ 300,000 for up to 1 year.
Phase II: $ 2 million for up to 3 years.
Background
Passive immunization by antibody administration has been used to prevent and/or treat several infectious diseases,
including RSV, hepatitis A and B, rabies, and COVID-19. The Antibody Mediated Prevention (AMP) trials established
proof-of-concept that delivery of a broadly neutralizing antibody (bNAb), VRC01, can protect against acquisition of bNAbsensitive HIV-1 strains. VRC01 has an excellent safety profile, does not depend on daily adherence for efficacy, and lacks
the side effects that can deter pre-exposure prophylaxis (PrEP) use. NIAID and its partners are building on the success of
the AMP trials by engineering next-generation bNAb candidates to enhance potency, increase tissue levels, extend half-life,
and contend with the ever-evolving global diversity of HIV-1. Effective antibody-based HIV prevention will require a more
potent combination of bNAbs with greater neutralization breadth than VRC01 and must target multiple sites of
vulnerability on the HIV Envelope (Env) glycoprotein. Developing bNAb cocktails presents additional challenges: complex
pharmacokinetics, larger injection volumes, multi-product formulations, and complicated manufacturing.
Currently, HIV-1 bNAb administration requires frequent injections. In the AMP trials, recipient acceptability of
intravenous (IV) administration was high. However, high cost and logistical burdens slowed the early uptake of monoclonal
antibodies for prevention and treatment of SARS-CoV-2, suggesting that IV administration can be challenging outside the
context of a clinical trial. Subcutaneous (SC) administration has low recipient acceptability due to local reactogenicity.
Improvements in bNAb delivery would benefit the field as NIAID and its partners develop the next generation of bNAbs
for HIV-1 prevention or other indications. Examples of devices and materials include, but are not limited to, dermal
patches, controlled-release hydrogels, nanoparticle carriers, vaginal rings, implantable devices, and nucleic acid delivery.
New or improved delivery devices and materials have the potential to increase end-user acceptability, increase adherence,
reduce administration-associated cost and time, and improve efficacy by maintaining sustained antibody titers.
