Knowledge about CanSino COVID-19 Adenovirus vector vaccine

Knowledge about CanSino COVID-19 Adenovirus vector vaccine.  Generally, inactivated vaccines are mainly to produce humoral immunity, and this is basically enough to protect the body.

▉ Introduction

In 2021.02.25, the State Food and Drug Administration has conditionally approved the registration application for the new coronavirus inactivated vaccine (Vero cell) of the Wuhan Institute of Sinopharm, and the recombinant new coronavirus vaccine (type 5 adenovirus vector) of Cansino Biotech. So far, there are 4 domestic vaccines for vaccination options (Table 1). From Table 1, we can see that of the 4 domestic vaccines on the market, 3 are Vero cell neo-coronavirus inactivated vaccines, and 1 is an adenovirus vector vaccine. Inactivated vaccines must be familiar to everyone. Today, let us briefly understand this unique adenovirus vector COVID-19 vaccine-(Ad5-nCoV).

▉ Adenovirus vector

Adenovirus vectors are developed from adenoviruses. Adenovirus is a large molecular double-stranded non-enveloped DNA virus (36 kb), which enters the cell through receptor-mediated endocytosis, and then the adenovirus genome is transferred to the nucleus, remains outside the chromosome, and does not integrate into the cell.

The host cell genome. Adenovirus is widely distributed in nature, and there are at least 100 serotypes. There are about 52 kinds of human adenoviruses, generally type 5 (Ad5) and type 2 (Ad2) as vectors. They are made by deleting the E1 gene necessary for virus replication and/or copying the non-essential E3 gene.

The one-sentence explanation is to allow the virus to infect human cells, but not to allow it to replicate. The carrier used by CanSino Bio’s recombinant COVID-19 vaccine is Ad5.

▉ Design principle and functioning mechanism

Transform the gene encoding the S protein in the COVID-19 vaccine into the adenoviral genome to form recombinant adenoviral particles (professional interpretation, non-professionals can ignore: the adenoviral vector system consists of the shuttle plasmid pCA13, the adenoviral genome plasmid pBHG11 and 293 cells (packaging cells). ) Composition.

The exogenous gene (the gene of the nCOVID-19 S protein) is introduced into the shuttle plasmid by restriction enzyme digestion and ligation. The pCA13 recombinant shuttle plasmid and pBHG11 are co-transfected into 293 cells (human embryonic kidney cell line integrating the Ad5 E1 gene), in the cell Homologous recombination occurs to form recombinant adenovirus particles.)

The protein shell of the virus has the same ability to infect cells as normal adenoviruses, but because the E1 gene in the genomic DNA is replaced by an exogenously introduced gene, it enters human cells After the virus cannot replicate, it only expresses the COVID-19 S protein, which reflects the safety of the adenovirus vector vaccine.

Adenovirus enters the host cell and releases its DNA into the nucleus. DNA is transcribed into mRNA, and mRNA is exported to the cytoplasm and translated into S protein, which in turn triggers humoral and cellular immune responses.

▉ Cellular immunity cannot be ignored

Generally, inactivated vaccines are mainly to produce humoral immunity, and this is basically enough to protect the body. But if the virus is too powerful, such as the new coronavirus. Some viruses that have not been killed by humoral immunity will sneak into human cells, and humoral immunity will be powerless. At this time, the advantages of cellular immunity will be manifested. Cellular immunity can dig out the latent viruses and wipe them out.

(Professional interpretation: refer to the above figure. Since adenovirus can infect almost all types of cells, when the S protein is expressed in MHC class I cells, it will be directly presented to CD8+ T cells through MHC I after antigen treatment. It is secreted to The extracellular S protein can be swallowed by macrophages, etc., and presented to CD4+ T cells through MHC II.

Of course, the virus can also be directly expressed in MHC II cells and presented to CD4+ T cells through lysosome treatment. .CD4+ T cells can change from Th0 state to Th1 or Th2 response by antigens, cytokines, and antigen-presenting cells. By secreting different cytokines, CD8+ T cells can be activated to become effector CTLs or B cells can be activated. Plasma cells or memory B cells.

When the new coronavirus really enters the body, the plasma cells will produce neutralizing antibodies to directly intercept the virus, and eventually be swallowed by macrophages. Viruses that escape the neutralizing antibodies will also be affected by the effector CTL after entering the cell It kills through the action of perforin and granzyme. The virus has nowhere to hide and cannot infect the body.)

▉ What are the advantages

The adenovirus vector COVID-19 vaccine produced by Cansino Bio has the characteristics of activating humoral and cellular immunity with only one shot of immunization. Stable existence at 2-8°C, easy storage and transportation, etc. all demonstrate the potential advantages of adenovirus vector system in vaccine development.

(source:internet, reference only)

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