Broadening sarbecovirus neutralization with bispecific antibodies combining distinct conserved targets on the receptor binding domain
Rattachement africain : nl, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Monoclonal neutralizing antibodies (mAbs) are considered an important prophylactic against SARS-CoV-2 infection in at-risk populations and a strategy to counteract future sarbecovirus-induced disease. However, most mAbs isolated so far neutralize only a few sarbecovirus strains. Therefore, there is a growing interest in bispecific antibodies (bsAbs) which can simultaneously target different spike epitopes and thereby increase neutralizing breadth and prevent viral escape. Here, we generate and characterize a panel of 30 novel broadly reactive bsAbs using an efficient controlled Fab-arm exchange protocol. We specifically combine some of the broadest mAbs described so far, which target conserved epitopes on the receptor binding domain (RBD). Several bsAbs show superior cross-binding and neutralization compared to the parental mAbs against sarbecoviruses from diverse clades, including recent SARS-CoV-2 variants. BsAbs which include mAb COVA2-02 are among the most potent and broad combinations. As a result, we study the unknown epitope of COVA2-02 and show that this mAb targets a distinct conserved region at the base of the RBD, which could be of interest when designing next-generation bsAb constructs to contribute to a better pandemic preparedness.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Broadening sarbecovirus neutralization with bispecific antibodies combining distinct conserved targets on the receptor binding domain
- Date Crossref
- 09/05/2024
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Amsterdam University Medical Centers pays non établi dans la noticeÉtablissement de santé
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Amsterdam institute for Immunology and Infectious Diseases pays non établi dans la noticeÉtablissement de santé
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University of Amsterdam pays non établi dans la noticeUniversité ou école supérieure
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Scripps Research Institute Department of Structural Biology and Computational Biology pays non établi dans la noticeOrganisation à but non lucratif
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Cornell University Department of Microbiology and Immunology pays non établi dans la noticeUniversité ou école supérieure
Amsterdam University Medical Centers, Amsterdam institute for Immunology and Infectious Diseases et University of Amsterdam, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.