CVR - Coronavirus Vaccines R&D Roadmap

Milestone
2.3.c

Antibody induction

In progress

Identify mechanisms underlying the induction of broadly protective antibodies, including the production and recall of long-lived memory B cells that recognize conserved coronavirus epitopes.

Progress Highlights

Germinal center responses—affinity maturation via somatic hypermutation; class-switch recombination, allowing B cells to switch from IgM to IgG, IgA, or IgE antibody types, diversifying functionality; and preferential selection of high-affinity clones—are key for the development of broadly neutralizing antibodies.

Yang 2023 found that induction of broadly protective antibodies is highly dependent on Tfh cells, which play a key role in driving affinity maturation of B cells.

Repeated antigen exposure through booster vaccination or hybrid immunity augments the selection of B cell clones that recognize conserved epitopes.

Roederer 2026 found that infection and breakthrough infection has been linked to the production of fusion peptide (FP)-directed antibodies that target epitopes conserved across sarbecoviruses. 

Depierreux 2026 found that while repeated RBD antigen exposure improved neutralization and somatic hypermutation, it did not improve antibody-dependent cellular cytotoxicity (ADCC). Instead, antibodies that target the S2 region were the strongest predictor of ADCC (particularly NK cell-mediated ADCC), whereas RBD and CTD targeting were the main predictors of neutralization.