Authors
Omar U. Guzmán-Bringas1,2, Keyla M. Gómez-Castellano1,2, Edith González-González1,2, Juana Salinas-Trujano1,2, Said Vázquez-Leyva1,2, Luis Vallejo-Castillo1,2, Sonia M. Pérez-Tapia1,2,3, and Juan C. Almagro1,4
Organizations
- Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico
- Laboratorio Nacional Para Servicios Especializados de Investigación, Desarrollo e Innovación (I + D + I) Para Farmoquímicos y Biotecnológicos, LANSEIDI-FarBiotec-CONACyT, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico
- Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico
- Department of Health Sciences and Technology, ETH Zürich, 8092 Zürich, Switzerland
- GlobalBio, Inc., 320 Concord Ave, Cambridge, MA 02138, USA
Abstract
We recently reported the isolation and characterization of anti-SARS-CoV-2 antibodies from a phage display library built with the VH repertoire of a convalescent COVID-19 patient, paired with four naïve synthetic VL libraries. One of the antibodies, called IgG-A7, neutralized the Wuhan, Delta (B.1.617.2) and Omicron (B.1.1.529) strains in authentic neutralization tests (PRNT). It also protected 100% transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from SARS-CoV-2 infection. In this study, the four synthetic VL libraries were combined with the semi-synthetic VH repertoire of ALTHEA Gold Libraries™ to generate a set of fully naïve, general-purpose, libraries called ALTHEA Gold Plus Libraries™. Three out of 24 specific clones for the RBD isolated from the libraries, with affinity in the low nanomolar range and sub-optimal in vitro neutralization in PRNT, were affinity optimized via a method called “Rapid Affinity Maturation” (RAM). The final molecules reached sub-nanomolar neutralization potency, slightly superior to IgG-A7, while the developability profile over the parental molecules was improved. These results demonstrate that general-purpose libraries are a valuable source of potent neutralizing antibodies. Importantly, since general-purpose libraries are “ready-to-use”, it could expedite isolation of antibodies for rapidly evolving viruses such as SARS-CoV-2.
CovalX Technology Used
Int. J. Mol. Sci. 2023, 24(5), 4609; https://doi.org/10.3390/ijms24054609