# Protection against lethal canine distemper virus infection by a dual epitope-targeting synthetic antibody

## TL;DR

Researchers developed a synthetic antibody that protects ferrets from lethal canine distemper virus infections, offering a new approach for antiviral therapies.

## Contribution

A dual epitope-targeting synthetic antibody was engineered to protect against CDV with a low dose.

## Key findings

- Two potent, neutralizing single domain antibodies were identified against the CDV H protein.
- A tetravalent and biparatopic antibody protected ferrets at a low dose of 1 mg/kg.
- The study highlights combining multiple neutralization mechanisms in a single therapeutic format.

## Abstract

Despite vaccine availability, the morbilliviruses measles virus and canine distemper virus (CDV) are still causing major health impairments in human and animal populations. Here, we identified two potent, neutralizing single domain antibodies directed against the tetrameric receptor binding (H) protein of CDV. Structural analyses spotlighted two vulnerable sites within the H protein. While the first overlaps with the receptor binding site, the second encompasses amino acid residues of two protomers located at the distal dimeric head interface, which supports distinct mechanisms of neutralization. Upon application of an engineered tetravalent and biparatopic antibody, ferrets were protected at a remarkably low antibody dose (1 mg/kg) administered intra-peritoneally on days 3 and 7 post-exposure of a lethal CDV challenge. Collectively, this study spotlights the power of integrating multiple mechanisms of neutralization in a single format and provides a roadmap to design next-generation therapeutics against morbilliviral infections as well as other infectious pathogens.

Measles virus and canine distemper virus (CDV) are still causing health impairments in humans and animals. Here, the authors develop a synthetic antibody protecting ferrets from lethal CDV infections, providing a roadmap for antiviral drug design.