Engineered Intranasal Virus Trap Provides Effective Protection Against SARS‐CoV‐2 Infection in Hamsters

Abstract

As face masks are no longer required in many public areas, SARS‐CoV‐2 continues to spread and pose health risks to vulnerable populations such as children, the elderly, and immunocompromised individuals. This study presents the development of an Fn‐LCB1‐based engineered intranasal virus trap (EIVT) designed to capture and neutralize multiple SARS‐CoV‐2 variants, limiting viral infection and transmission. Fn‐LCB1, a fusion protein consisting of an Fn domain that binds to fibronectin and an LCB1 domain with high affinity for the Spike protein receptor‐binding domain (RBD) of SARS‐CoV‐2 viruses, can be produced on a large scale and purified in soluble form with high thermal stability. In vitro experiments demonstrated the efficient neutralization of SARS‐CoV‐2 wildtype and several variants, including Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) by Fn‐LCB1. Additionally, Fn‐LCB1 effectively protected against SARS‐CoV‐2 Delta infection in a noncontact viral transmission Syrian hamster model. This study establishes Fn‐LCB1 as a potent prophylactic agent against SARS‐CoV‐2 in vitro and in vivo, and serves as a proof‐of‐concept for the application of intranasal proteins to capture respiratory viruses and reduce live cell infections by competing with viral receptors.

Virus-Mimetic Extracellular-Vesicle Vaccine Boosts Systemic and Mucosal Immunity via Immune Recruitment

“…Not only does the continuous emergence of variants evade protective antibodies generated from previous natural infection or vaccination but also the level of antibodies in the human respiratory tract is hundreds of times lower than that in peripheral blood, enabling SARS-CoV-2 to anatomically escape at the site of initial infection and replicationthe respiratory tract mucosa. − Consequently, respiratory viruses, such as SARS-CoV-2 and influenza viruses, that are responsible for nonsystemic infections, frequently cause recurrent infection. The efficacy of current vaccines has declined, necessitating frequent booster shots. , In response to these challenges, there is an urgent need to develop a vaccine that induces localized broad-spectrum protective immunity in the respiratory tract, offers excellent safety, and is widely accepted by the public. − …”