Development of Nanobody-Expressing Nanosomes for Neutralization of Influenza Virus

Abstract

Influenza viruses remain a persistent threat to both human and animal health, whereas current countermeasures-vaccination and livestock culling-offer only delayed, partial, or economically burdensome protection. Here, we describe the development of a mucosal nanotherapy based on chromosome-free minicells derived from Lactiplantibacillus plantarum, engineered to surface-display a broadly reactive anti-hemagglutinin nanobody. These therapeutic agents, termed "neutralizing nanosomes" present nanobody molecules anchored on the minicell surface that retain full binding functionality against a broad spectrum of influenza viruses, including H1N1. Importantly, intranasal administration of neutralizing nanosomes effectively neutralized H1N1 infection in vivo, alleviating physiological symptoms and suppressing viral replication in the respiratory tract of a preclinical mouse model. Unlike vaccines, which require weeks to confer protection, our neutralizing nanosomes provide an immediate barrier at the respiratory mucosa-the primary portal of influenza entry- offering a promising adjunct to existing vaccines and antiviral drugs.