Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike’s receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.

Antigenic variation and viral evolution have thwarted traditional influenza vaccination strategies.The broad protection afforded by a "universal" influenza vaccine will come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use non-circulating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These "resurfaced" HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals.Through structure-guided optimization we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and H1/H3 cross-reactive bnAbs with high affinity. Subsequent serological analyses from murine prime-boost immunizations show that the rsHAs are both immunogenic and can enrich for RBS-directed antibodies. Our structure-guided, RBS grafting approach provides candidate immunogens for selectively presenting a conserved viral epitope. MAIN TEXTInfluenza evolves primarily at the human population level and within its animal reservoirs (swine and avian) 1 . Host humoral pressure, which predominantly targets the viral hemagglutinin (HA), selects for influenza mutations that render previous immune responses suboptimal. The humoral response then evolves, through immune memory and further B cell affinity maturation [2][3][4][5] . The net effect of this on-going selection across the entire population exposed to the virus is a virusimmunity "arms race". The repeated exposure to influenza in the human population results in preexisting immunity which influences subsequent immune responses [6][7][8][9][10][11] . This immunological memory 12,13 presents a significant hurdle towards the development of a "universal" influenza vaccine. Strategies are necessary that both overcome the recall of refined, strain-specific responses and elicit broadly neutralizing antibodies (bnAbs). bnAbs against influenza HA target two relatively invariant epitopes the receptor binding site (RBS) on the HA "head" and a surface along the HA "stem" 14 . While stem-directed immunogens are in clinical development, efforts focusing on the RBS have lagged behind 14 . A significant challenge for RBS-directed immunogens is presentation of the complex RBS structure that includes multiple