In vivo delivery of a highly neutralizing antibody against Zika virus using microneedles.

Abstract

Zika fever is caused by a flavivirus named Zika virus (ZIKV), which belongs to the Flaviriridae family. This virus has been linked to a significant increase in the number of babies born with microcephaly due to maternal infection. Monoclonal antibodies (mAbs) have been widely used for treating viral infections; however there is currently no licensed mAb for ZIKV control. Previous studies conducted by our group have characterized, both in vitro and in vivo, a fully human anti-Zika mAb (A9Z) that can recognize the envelope (E) protein of ZIKV, demonstrating significant protective potential in both prophylactic and therapeutic strategies. Microneedles (MNs) represent an innovative approach to antibody delivery, offering several advantages over traditional delivery methods, providing sustained and controlled release of the antibody over time. In this project, we aim to use MNs for the safe and controlled delivery of A9Z directly into the skin, testing different MN-A9Z mAb formulations. The main aim of this project is to evaluate the protective efficacy of various formulations of the mAb A9Z functionalized in the MNs in prophylactic and therapeutic settings. Our project involves refining the MN prototype for A9Z delivery, assessing its stability and safety, and testing different formulations in prophylactic and therapeutic models to enable the therapeutic delivery of the mAb via MNs in a controlled and sustained manner, effectively reducing the viral load in mice infected with the virus and maintaining therapeutic levels of the antibody in the bloodstream. (AU)