This cover image shows the sequences encoding the spike protein of SARS-CoV-2, the causal agent of COVID-19. COVID-19 has caused a large-scale global outbreak and has become a major public health issue. As an essential part in the viral entry of SARS-CoV-2, the spike protein is a target for vaccine and drug development. Researchers have designed a recombinant adenovirus type-5 (Ad5)-vectored COVID-19 vaccine based on spike protein genes, which encodes the full spike protein. After a single immunization in phases I and II of human clinical trials, the Ad5-vectored COVID-19 vaccine has demonstrated favorable safety and immunogenicity profiles and has been shown to induce rapid humoral and T-cell responses. The results from the published clinical studies are promising and pave the way for efficacy trials.