Using high-resolution mass spectrometry, researchers have mapped glycan-processing states of the spike protein complex that allows the SARS-CoV-2 virus to infect human cells - finding that SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in vaccine design. As scientists seek to combat the virus that causes COVID-19, the development of vaccines has focused on the spike, a protein complex composed of three protomers that protrudes from the virus and binds to the ACE2 receptor on the surfaces of human cells. Each protomer harbors 22 chemical sites that can undergo glycosylation, a biochemical reaction that adds a glycan compound to a protein. How these sites are glycosylated may affect which cells the virus can infect. The same processes could also shield some regions on the spike from being neutralized by antibodies. Seeking insight, Yasunori Watanabe et al. expressed and purified recombinant glycosylated spike complexes, then used enzymes to cut them into peptides each containing a single glycan but representing all glycan sites. The researchers then used a technique called mass spectrometry to determine the glycan composition at each site. They report that the SARS-CoV-2 S protein is less densely glycosylated than some other viral glycoproteins, possessing a sparse "glycan shield," which may be beneficial for the elicitation of potent neutralizing antibodies. Their analysis provides a benchmark that can be used to measure the quality of the spike antigen as researchers develop new vaccines and antibody tests.