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.