to be given to the choice of the antigen. Care also has to be taken to assure that the

immunogenicity of the chosen candidate is maintained once isolated from its natural

environment [13]. Several avenues of research are focused on identifying the most

immunogenic viral sub-unit that could serve as an antigen and also how to maintain

its immunogenicity during large-scale production and delivery [11].

When using a protein antigen, for instance, in the case of SARS-CoV-2, the

Spike protein is an obvious choice since it is responsible for cell entry (Figure 3.16).

The virus uses the spike protein to bind a cell surface protein, acetylcholine esterase

2 (ACE-2), to gain entry into the cell. Therefore, a neutralizing or protective an-

tibody could be one that would disrupt this interaction reducing the ability of the

virus to enter the target cell. While it is possible to use the entire spike protein, there

are attempts to use just the part that interacts with the receptor, since in theory, it

should be able to elicit the desired effect.

Regardless of the protein fragment that serves as the antigen, it can be delivered,

either as a protein, or as a nucleic acid (DNA or RNA) fragment that can then be

used as a template to produce the protein in the host [14].

3.4.5

DNA VACCINE

Once the antigen to be used in a vaccine has been identified, it is straightforward to

determine the corresponding DNA sequence and use it to create a recombinant

DNA molecule carrying an expression cassette for the protein in question. This

DNA can be injected into the tissue, where it is taken up by the patient’s cells that

start producing the protein. The route of administration can vary. The DNA can be

FIGURE 3.16 SARs-CoV-2 spike protein. The figure shows the interaction between the

SARs-CoV-2 spike protein with the ACE-2 (acetylcholine esterase 2) receptor on a target

cell.

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Bioprocessing of Viral Vaccines