The development of several highly efficacious vaccines against a previously unknown viral pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in less than 1 year from the identification of the virus is unprecedented in the history of vaccinology.

Two activities predate the successful COVID-19 vaccines: the utilization of highly adaptable vaccine platforms such as RNA (among others) and the adaptation of structural biology tools to design agents (immunogens) that powerfully stimulate the immune system.

The discovery of an immunogen adaptable to the multiple platforms (messenger RNA and others) used for COVID-19 vaccines resulted from collaboration across different scientific subspecialities.

Although this sophisticated approach has not yet led to a successful HIV vaccine, it caught the attention of another VRC investigator, Barney Graham, who was interested in generating a vaccine for respiratory syncytial virus (RSV).

They identified the prefusion conformation of the viral spike protein as highly immunogenic and created mutations to stabilize that conformation for successful use as an immunogen.

So, when the genetic sequence of the SARS-CoV-2 became available, Graham's team lost no time in joining their long-time collaborators at Moderna to develop an RNA vaccine using a stabilized, prefusion spike protein as the immunogen.

Pfizer and BioNTech, where Karikó was working, also used the RNA platform that she and Weissman had perfected and the immunogen designed by Graham to develop an RNA vaccine.

Additional companies also used Graham's immunogen in other vaccine platforms that had been evolving for years, to make SARS-CoV-2 vaccines.

Several of these vaccines were tested in phase 3 efficacy trials at a time when the level of community spread of SARS-CoV-2 was extremely high, allowing vaccine efficacy endpoints of greater than 90% to be reached in a timely fashion.