Prototype DNA vaccines for SARS-CoV-2: The development of a vaccine to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent biomedical need. Yu et al. designed a series of prototype DNA vaccines against the SARS-CoV-2 spike protein, which is used by the virus to bind and invade human cells. Analysis of the vaccine candidates in rhesus macaques showed that animals developed protective humoral and cellular immune responses when challenged with the virus. Neutralizing antibody titers were also observed at levels similar to those seen in humans who have recovered from SARS-CoV-2 infection. Science , this issue p. 806

How an early variant got ahead: Throughout the COVID-19 pandemic, epidemiologists have monitored the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with particular focus on the spike protein. An early variant with an aspartic acid (D) to glycine (G) mutation at position 614, D614G, rapidly became dominant and is maintained in current variants of concern. Zhang et al. investigated the structural basis for the increased spread of this variant, which does so even though it binds less tightly to the host receptor (see the Perspective by Choe and Farzan). Structural and biochemical studies on a full-length G614 spike trimer showed that there are interactions not present in D614 that prevent premature loss of the S1 subunit that binds angiotensin-converting enzyme 2. This stabilization effectively increases the number of spikes that can facilitate infection. Science , this issue p. 525 ; see also p. 466

Delta’s spike: Understanding the molecular mechanisms of the increased transmissibility and immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is critical to guiding current and future intervention strategies. Zhang et al . determined cryo–electron microscopy structures of the full-length spike protein trimers of the Delta, Kappa, and Gamma variants of SARS-CoV-2 and studied their function and antigenic properties. The Delta spike protein fused membranes more efficiently at low levels of the cellular receptor ACE2, and its pseudotyped viruses infected target cells substantially more rapidly than all other variants tested, possibly at least partly accounting for its heightened transmissibility. Mutations of each variant rearranged the antigenic surface of the N-terminal domain of the spike protein but only caused local changes in the receptor-binding domain, consistent with greater resistance to neutralizing antibodies. These findings elucidate the molecular events that have led these viruses to adapt in human communities and to evade host immunity. —VV