From Immunogen to COVID-19 vaccines: Prospects for the post-pandemic era

Abstract

The COVID-19 pandemic has affected millions of people and posed an unprecedented burden on healthcare systems and economies worldwide since the outbreak of the COVID-19. A considerable number of nations have investigated COVID-19 and proposed a series of prevention and treatment strategies thus far. The pandemic prevention strategies implemented in China have suggested that the spread of COVID-19 can be effectively reduced by restricting large-scale gathering, developing community-scale nucleic acid testing, and conducting epidemiological investigations, whereas sporadic cases have always been identified in numerous places. Currently, there is still no decisive therapy for COVID-19 or related complications. The development of COVID-19 vaccines has raised the hope for mitigating this pandemic based on the intercross immunity induced by COVID-19. Thus far, several types of COVID-19 vaccines have been developed and released to into financial markets. From the perspective of vaccine use in globe, COVID-19 vaccines are beneficial to mitigate the pandemic, whereas the relative adverse events have been reported progressively. This is a review about the development, challenges and prospects of COVID-19 vaccines, and it can provide more insights into all aspects of the vaccines.

Keywords: Adverse reactions; COVID-19; Complications; Contraindications; Vaccine.

Graphical abstract

Fig. 1

This figure illustrates the cascade immune response, the endogenous protein synthesized by COVID-19 in the host cells activates and promotes the proliferation of specific CD8 +T cells through MHC-Ⅰ, which produce cytotoxic effects on the target cells. CD4 +T cells can differentiate into different Th cells（include Th1, Th2, Th17 and Treg） through the binding of MHC-II antigen complex of antigen presenting cells(APC). The massive replication of COVID-19 activates CD4 +T cells to differentiated into Th1 cells, which can secrete a large number of proinflammatory factors, such as IL-6, IFN-γ and granulocyte macrophage colony-stimulating factor (GM-CSF). B cells can be activated by Th1 and produce IL-6 and IgG and IgM. GM-CSF induces monocytes to differentiated into M1 macrophages, which produce IL-6, IL-18, iNOS and a large number of inflammatory chemokines and increase glycolysis in the tissues, while the released lactic acid can further damage the cytolytic ability of CD8 +T cells. CD4 +T cell can also differentiate into Th2, which secrete IL-4, IL-10, TGF-β and other anti-inflammatory factors, inhibit the proliferation of T cells and induce monocytes to transform into M2 macrophages. On the other hand, TGF-β and IL-6 can induce the expression of expression of RORγT and promote CD4 +T cells to differentiate into Th17, which can secrete proinflammatory cytokines, such as IL-17, IL-21 and IL-22. The cytokines thereby further promote the differentiation and proliferation of Th17 and enhance the inflammatory response and autoimmune response. TGF-β can also induce the expression of forkhead box P3 (FoxP3) and promote the differentiation of CD4 +T cells into Treg, which secretes TGF-β and IL-10.

Fig. 2

The World Health Organization (WHO) maintains a working document that includes most of the vaccines (until September 30, 2022) in clinical and pre-clinical development. Available from: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines.

Fig. 3

This figure illustrates the principles of different vaccines. nucleic acid vaccines are relatively complex. DNA vaccines need to enter the nucleus of host cells to further synthesize corresponding immunogenic proteins. mRNA can synthesize corresponding immunogenic proteins after entering the cytoplasm of host cells, the protein coded by nucleic acid vaccines can induce immune response after being secreted by host cells; virally vector vaccines contains virtual vector vaccines (non replicating) and virtual vector vaccines (replicating). Both live attenuated vaccine and vector vaccines (replicating) have the ability of duplication. Totally, the protein subunit vaccine, the protein coded by nucleic acid vaccines and virtual vector vaccines, live attenuated vaccine, inactivated vaccine, virally vector vaccines and virus like particles vaccine can be recognized by antigen presenting cells (APCs), which can further activate CD4 +T cells through MHC-II antigen complex. The memory B cells and memory CD8 +T cells will be produced by the cascade immune response caused by vaccines.