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Pandemic Preparedness Resources

Rapid discovery of neutralizing monoclonal antibodies for first line defense

PI(s)/Head responsible for the resource:

Gunilla Karlsson Hedestam

Host organisation(s):

Karolinska Institutet

Resource description:

With the ongoing SARS-CoV-2 pandemic, there is a need to identify broadly neutralizing monoclonal antibodies (mAbs) that can be used as first-line defense against newly emerging variants. Already in the first year of the pandemic, the scientific community showed that highly effective neutralizing mAbs can be isolated from convalescent donors, some of which were rapidly approved for clinical use. Because of their exquisite specificities, monoclonal antibodies are generally safe and rarely give side effects. Furthermore, by targeting conserved epitopes on the virus spike, antibodies that resist changes in the virus can be identified. We recently developed a high throughput technique to clone large numbers of human antibody heavy and light chains from single-sorted memory B cells, for subsequent expression in mammalian cells. In collaboration with the Murrell group at KI, we screened the mAbs for their neutralizing activities against a panel of SARS-CoV-2 variants. Of several evaluated mAbs, we identified antibodies that cross-neutralize all SARS-CoV-2 variants of concern, including the recent Omicron sub-variants, BA.5 and BA2.75. Furthermore, in collaboration with the Hällberg group at KI, we determined high resolution structures of some of the most interesting mAbs by cryo-EM. These studies reveal the mode of antibody binding to the SARS-CoV-2 spike and demonstrate how B cell affinity maturation increases the potency and breadth of antibody neutralizing activity.

Contact information:

Gunilla Karlsson Hedestam