Engineering Sustained-Release Broadly Neutralizing Antibody Formulations

Area of Science:

• Biomaterials Science
• Immunology
• Pharmacology

Background:

• Sustained serum levels of broadly neutralizing antibodies (bnAbs) are essential for effective passive immunization against infectious diseases.
• Poor pharmacokinetics (PK) and administration challenges hinder the clinical use of bnAbs for prophylaxis.
• Novel delivery systems are needed to prolong bnAb circulation and efficacy.

Purpose of the Study:

• To engineer a polymer-nanoparticle (PNP) hydrogel depot for sustained protein delivery.
• To investigate the impact of hydrogel properties and biological factors on bnAb pharmacokinetics.
• To predict human PK profiles for bnAb delivery using hydrogel technology.

Main Methods:

• Development and characterization of PNP hydrogel depots for protein delivery.
• In-vivo studies in mice and rats to assess prolonged protein release.
• Flow cytometry to analyze immune cell infiltration and antibody release mechanisms.
• Multicompartmental modeling to predict human PK profiles.

Main Results:

• PNP hydrogel depots demonstrated prolonged release of antibody cargo in animal models.
• Immune cell infiltration into the hydrogel led to faster-than-expected antibody release via active transport.
• Co-formulation with an anti-inflammatory agent reduced cellular infiltration, extending delivery duration.
• Predicted human PK profiles suggest potential for long-term immunoprophylaxis with subcutaneous hydrogel injection.

Conclusions:

• Engineered PNP hydrogel depots can significantly prolong the pharmacokinetics of bnAbs.
• Controlling immune cell infiltration is key to optimizing hydrogel-based antibody delivery.
• This technology offers a promising platform for developing next-generation long-acting immunoprophylaxis strategies.