11. Subunit vaccines
Purified viral antigen peptides such as the S protein of the SARS-CoV2 can be manufactured in various in vitro expression systems and applied as safe vaccine candidates. The vaccinated peptide is then processed and delivered in the context of MHC class ΙΙ, and despite the weak CD8+ T cell induction (Fig. 2) (Table 3) [27], it provides strong stimulation to helper CD4+ T cells and antibody production. Therefore, employment of adjuvants and repeated doses is recommended to stimulate as much immunity in this generation of vaccines. Subunit vaccines are the most common platform of vaccine used to cope with COVID-19 infection, with 20 candidates in clinical trial evaluation and 62 other vaccines in the preclinical development (44). Most of these vaccines contain all or part of the S protein, which like the SARS and MERS vaccines, induce neutralizing antibody responses [107, 108]. One of the positive points of subunit vaccines is the focus of neutralizing antibody responses towards immunodominant epitopes and deflecting of ADE occurrence [109]. Nevertheless, the proteins and peptides encompassing in subunit vaccines can elicit appropriate responses when their expression, translation and glycosylation were ensued in mammalian eukaryotic systems [110]. Besides, the protein subunit vaccines are unsuitable for mucosal vaccination and the use of unmodified alum adjuvants runs the risk of Th2 responses [96] and fueling the ADE phenomenon [111]. Based on this, 2 COVID-19 subunit vaccines produced by Novavax and GlaxoSmithKline (GSK) companies have employed Matrix-M and AS03 adjuvants to stimulate immune responses, respectively [2]. EpiVacCorona is another leading protein subunit vaccine containing aluminum hydroxide which has been in phase ΙΙΙ of the clinical trial since November in Russia. In another effort a recombinant new protein subunit coronavirus vaccine as the joint product of Anhui Zhifei Longcom Biopharmaceutica and Institute of Microbiology, Chinese Academy of Sciences was designed by CHO cell-expressed full length S1-human IgG1 Fc fusion protein. Surprisingly, this candidate primed remarkable neutralizing anti-S1 antibody responses in rabbits, mice and macaques [112]. Other candidates are passing through phase I and II clinical trials.