A Review of Virus-Like Particle-Based SARS-CoV-2 Vaccines in Clinical Trial Phases

The Coronavirus disease 2019 (COVID-19) pandemic has affected more than 269 million worldwide, with more than five million deaths as of early December 2021. The main concerns in this pandemic include the asymptomatic nature of COVID-19, leading to the infection of many healthy people, the infectious nature of the pathogen, and its high spreading rate. The disease features have highlighted the importance of controlling this pandemic via vaccines. There has been a worldwide race to produce better, more protective, and efficacious vaccines. Simultaneously, different new variants of the virus are emerging. Therefore, there is a concern about the efficacy of the vaccines against new variants. The platform used for COVID-19 vaccine development needs to be flexible enough to enable the manufacturer to react suitably to new virus variants. We performed a comprehensive search in the online databases of PubMed, Scopus, Google Scholar, clinicaltrials.gov, WHO, ICTRP, and Cochrane until December 10th, 2021. There are 331 candidate vaccines in clinical development, with 194 in the preclinical stage and 137 in different clinical phases. Eleven platforms have been used for the development of COVID-19 vaccines, including inactivated/live attenuated virus, protein subunit, virus-like particle (VLP), non-replicating/replicating viral vectors (VVnr or VVr), VVr or VVnr plus antigen-presenting cell, bacterial antigenspore expression vector, DNA, and RNA. The VLP-based vaccine platform is a safe, highly immunogenic, and flexible platform for developing vaccines. This review focuses on VLP-based vaccine platforms and explicitly discusses the six VLP-based COVID-19 vaccines in clinical trial phases.