Abstract
COVID-19 pandemic has been the deadliest infectious disease outbreak since Spanish flu. The emerging variant lineages, decay of neutralizing antibodies, and occur of reinfections require the development of highly protective and safe vaccines. As currently approved COVID-19 vaccines that utilize virus-related genetic material are less than ideal, other vaccine types have been also widely investigated. Among them, peptide-based vaccines hold great promise in countering COVID-19 as they may overcome most of the shortcomings of RNA/DNA and protein vaccines. Two basic types of potential peptide vaccines can be developed. The first type are those which rely on cytotoxic T-cell (CTL) responses to kill infected host cells and stop the replication via employing CTL-epitopes as vaccine antigens. The second type of peptide vaccines are those that rely on B-cell peptide epitopes to trigger humoral response via generating SARS-CoV-2-specific antibodies to neutralize and/or opsonize the virus. We propose that combining both cellular and humoral immune responses would be highly protective. Here we discuss opportunities and challenges in the development of an effective and safe peptide-based vaccine against COVID-19.