Recombinant DNA Vaccines: Defenders against COVID-19

by Gerardo Luiz Sison (Hachimoji)

The COVID-19 pandemic has devastated the world’s population for more than a year, and as the world combats the disease, many institutions have developed different vaccines. Vaccine production employs many viable strategies, in which the use of recombinant DNA (rDNA) technology provides a novel type of vaccine.

The coronavirus and its structure

COVID-19 is a flu-like respiratory syndrome caused by a virus called SARS-CoV-2—a single-stranded RNA virus belonging to the Coronaviridae family, commonly called coronaviruses.

Like all coronaviruses, SARS-CoV-2 comprises a spherical envelope surrounding a core membrane made of matrix protein. This core further encloses a single strand of positive-sense RNA associated with nucleoprotein. 

The SARS-CoV-2 structure. (Source: Singh, R. B. (2021). SARS-CoV 2 Structure. StatPearls Publishing LLC.)

The spike proteins (S1 and S2) on the outermost layer of the virus act as access keys to our cells. The S1 subunit of the spike protein interacts with the angiotensin-converting enzyme 2 (ACE2) protein on our cell surfaces, after which the S2 subunit aids membrane fusion between virus and host, allowing viral entry into our cells.

Vaccine production through recombinant DNA technology

This mechanism of interaction between the spike proteins and ACE2 human cell proteins provides a way for researchers to employ rDNA technology in creating a vaccine. First, we identify the gene which codes for spike protein creation, then insert that gene into a safer, common virus, such as an adenovirus, for delivery into human cells. This safer virus, which now contains the spike protein gene, can now be injected into human bodies. Hence, the viral vector vaccine produced by rDNA technology.

Upon it is first introduced into a host, the body takes up pieces of the pathogen and displays them on cellular surfaces to build long-term immunity against any disease. Specialized immune cells recognize these pieces, called antigens. These produce pathogen-specific agents, called antibodies, which surround incoming pathogens to inhibit their interaction with our cells, preventing further infection. The antibodies also act as signals for the immune system to produce more antibodies or to destroy cells that have the antigens on their surfaces. The body then remembers how to make these antibodies in the event of future infections by the same pathogen, heightening the immunity of the person.

Vaccine developers produce the viral vector in such a way that it cannot multiply by itself. Its primary function is to insert the spike protein gene into the host cell's nucleus. From there, the host cell machinery recognizes the gene and stimulates production of the spike protein. These spike proteins then act as antigens that trigger the aforementioned immune responses. 

How it differs from other vaccine types

Other major types of vaccines that have reached human trials or have been allowed for emergency use include inactivated vaccines, protein subunit vaccines, and DNA/RNA-based vaccines. While the general goal is to induce immune responses, these vaccines work in different ways to offer protection, each with corresponding advantages and disadvantages.

Studies have shown that among its advantages is that rDNA vaccines are more flexible than other types of vaccines in terms of producibility, since we can insert it into multiple types of hosts. Recent advances in genetic engineering have enhanced the management of rDNA vaccine production. Compared to inactivated vaccines, rDNA vaccines also ease the need for post-vaccination treatment.

However, the major disadvantage of this type of vaccine is its high production cost, rendering it inefficient for low-income countries. It would take high amounts of the rDNA vaccine to successfully mediate immunological action in the body, which adds to its expensiveness. Immunogenicity is also commonly low when they administer a lone rDNA vaccine, thus, they provide immune response boosters called adjuvants alongside the vaccine for immunoresistance. This adds a monetary weight to the use of rDNA vaccines. Nevertheless, its high efficiency and the availability of bioengineering technology provide solid ground for the evolution of rDNA vaccine development and research in future years to come, challenging the scientific field to find breakthroughs in order to nullify its disadvantages.


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