SARS-CoV-2-mediated immune system activation and potential application in immunotherapy

Abstract

Although novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated pulmonary inflammation has recently attracted great attention, its pathology and pathogenesis are not clear. Notably, due to both its high infective and pathogenicity, SARS-CoV-2 infection may cause a severe sometimes fatal respiratory disease. A specific vaccine, which relies on the analysis of SARS-CoV-2 structural protein-derived antigenic peptides, is indispensable for restraining the spread and reducing the mortality of SARS-CoV-2. SARS-CoV-2 infections activate cytototxic, myeloid-derived suppressor cells, dendritic cells, macrophages, as well as natural killer, B, helper T, and regulatory T cells, thus further stimulating innate and antigen-specific immune responses. Nevertheless, many immune effector cells cause hyperinflammation and pulmonary immunopathology by releasing proinflammatory cytokines and chemokines, including interferon (IFN)-α, IFN-β, IFN-γ, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1A, MIP1B, interleukin (IL)-1, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-12, IL-17, and IL-18, platelet-derived growth factor, fibroblast growth factor, tumor necrosis factor-α, and induced protein 10. Interestingly, related products derived from SARS-CoV-2 are likely to trigger immune evasion. Therefore, investigating SARS-CoV-2-specific vaccines, blocking immunopathology, and prohibiting immune evasion are urgently required for treating SARS-CoV-2 infection. In this review, we emphatically illuminated the development of a SARS-CoV-2-specific vaccine based on the analysis of epitopes, also expounding the molecular mechanisms of SARS-CoV-2-mediated cytokine release syndrome. Furthermore, we comprehensively discussed SARS-CoV-2-associated immune evasion and lung immunopathology. Lastly, potential therapeutic strategies against SARS-CoV-2 were explored.

Keywords: SARS-CoV-2; epitopes; immunopathology; inflammation; molecular mechanisms; vaccine.