Devices and Materials-Based Platforms for the Delivery of Broadly Neutralizing Antibodies

Fast Track proposals will be accepted. Direct-to-Phase II proposals will not be accepted. Number of anticipated awards: 2-4 Budget (total costs): Phase I: $ 300,000 per year for up to 2 years Phase II: $ 2 million total for up to 3 years Background Passive immunization by antibody administration has been used to prevent and/or treat several infectious diseases, including Respiratory Syncytial Virus (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 the acquisition of bNAb-sensitive 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 use of pre-exposure prophylaxis (PrEP). 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. Under these contract awards, the delivery platforms can additionally be extended to these infectious diseases: Respiratory Syncytial virus (RSV), Malaria, Herpes Simplex Virus (HSV), Ebola virus, and Nipah virus. 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.