A group of researchers has determined how different proteins associated with SARS-CoV-2 - the virus that causes COVID-19 - generate immune responses when given to rabbits as immunizations. According to the authors, the results provide "a better understanding of the quantitative and qualitative aspects of immune response generated by different vaccine antigens ... which could greatly benefit the development and evaluation of SARS-CoV-2 therapeutics and vaccines." In the ongoing quest for a COVID-19 vaccine, scientists have identified the viral spike protein complex - the surface structure that allows the virus to enter human cells through the ACE2 receptor - as the most promising base for a successful vaccine. But researchers still do not fully understand how the spike protein generates responses from the immune system, and whether these responses correlate with protection. Seeking insight, Supriya Ravichandran and colleagues immunized rabbits with one of four SARS-CoV-2 spike protein antigens similar to those being used in clinical trials. The authors observed that antibodies from animals immunized with the receptor-binding domain (RBD, which is key for the virus' ability to bind ACE2 and has been included in most spike protein vaccines), the S1 domain, or the S1+S2 ectodomain neutralized as many as 98% of SARS-CoV-2 virions after two vaccinations. Importantly, the RBD immunization was the most effective option, as it generated more high-affinity antibodies than the vaccines based on either S1 or the S1+S2 ectodomain. The researchers did not directly test their vaccine's protective capabilities in the rabbits, but say that the ability to elicit high-affinity antibodies may enhance the protective properties of vaccines for COVID-19.