Novel, Cross-Sarbecovirus Neutralizing and Binding Monoclonal Antibodies (mAbs) (HJF 660-23)

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine elicited protection highlights the need to develop vaccine candidates with broad protection. Current invention identified six neutralizing antibodies with broad sarbecovirus cross-reactivity. This finding has applications towards developing next-generation vaccine candidates that confer broad protection against SARS CoV-1 and SARS-CoV-2 variants.

Applications and Advantages

Diverse array of novel mAbs that are cross-sarbecovirus binding and neutralizing
Critical for understanding neutralizing epitopes
Important tools for future vaccine design and vaccine strategies

Innovation Description

Researchers at the Henry M. Jackson Foundation (HJF) and Walter Reed Army Institute of Research (WRAIR) have identified cross-sarbecovirus neutralizing and binding mAbs including 39 cross-sarbecovirus neutralizing mAbs generated from the sorted and sequenced B cell receptors (BCRs) from a Phase I clinical trial participant.

Text Box: Fig.1 Thirty-nine neutralizing mAbs, isolated post 3rd SpFN dose showed neutralization breadth against SARS-CoV-2 variants and some to SARS-CoV-1 The participant was given two or three doses of the Spike Ferritin Nanoparticle (SpFN) SARS-CoV-2 vaccine. These mAbs identified after vaccination target Spike protein neutralization domains including the receptor binding domain (RBD) and N-terminal domain (NTD) to WA-1 and across SARS-CoV-2 and CoV-1 variants (Fig. 1).
Knowledge of these vaccine-targeted binding sites (epitopes) could inform future vaccine designs and vaccine strategies that elicit neutralizing mAbs towards a wider breadth of human coronaviruses. Currently, there is no cross-sarbecovirus neutralizing mAb used clinically. Hence this invention could prove to be a valuable tool in developing next-generation vaccine candidates that confer broad protection against several SARS virus variants.

Figure 1: Fig.1 Thirty-nine neutralizing mAbs, isolated post
3rd SpFN dose showed neutralization breadth against
SARS-CoV-2 variants and some to SARS-CoV-1

Inventors

Kerri G. Lal, Ph.D., HJF
Shelly J. Krebs, Ph.D., WRAIR
Samantha Townsley, Ph.D., HJF
Michael G. Joyce, Ph.D., HJF
Vincent Dussupt, Ph.D., HJF

Innovation Status

These antibodies were tested for in vivo protection, structural analysis and binding and neutralization across diverse sarbecovirus and SARS-CoV-2 variants of concern (VoC). Please see Nature Comm 2024 Jan 03; (15):200 ; Sci. Transl.Med. 2022 Feb 16; 14(632):eabi5735