IT HAS happened all too quickly: within a year since the beginning of the COVID-19 pandemic, vaccines are already getting approval and being used worldwide. But as much as these vaccines have given hope, they have generated a significant amount of concern. The vaccines have been developed within a tenth of the standard development process, and it is the first time an mRNA vaccine has been approved. However, by cultivating our understanding of these vaccines, we might be able to mitigate our unease.

How vaccines work

   Vaccines work closely with our adaptive immune system, which is in charge of responding and defending against a specific pathogen[1]. The basis of the adaptive immune response lies in its ability to create antibodies that selectively target an antigen[2], such as a spike on the surface of a virus. Once the antibodies detect and attach to a corresponding spike, they can neutralize the viral particle or call over phagocytes, which are cells that engulf and degrade the pathogen. Simultaneously, the blueprint for making these antibodies is “stored” in cells called memory cells; the body will be ready for whenever the same or similar pathogen enters it again[3].

    Vaccines aim to build the same immune defense that the body naturally makes when infected with a pathogen but without exposing it to the disease. The oldest types of vaccines involve the injection of inactivated or neutralized (live attenuated) viruses. Upon injection, the body develops an immune response against these inactive viruses as if the actual viruses have infected the body. These vaccines are called “first-generation vaccines,” and notable examples include the MMR vaccine, which immunizes against measles, mumps, and rubella[4].

   However, for the COVID-19 vaccines, developers have geared their focus on the newer second and third-generation vaccines. Novavax’s COVID-19 vaccine is an example of a second-generation vaccine, which injects just parts of the virus—also known as “immunogenic virus-like nanoparticles.” These vaccine particles resemble certain virus subunits and are engineered to produce an immune response against those specific parts of the virus[5]. While first and second-generation vaccines have been extensively experimented with for decades, it is the third- generation vaccines that have been the subject of research and public scrutiny during the pandemic.

The third generation vaccines

    The two major classes of third-generation vaccines—also known as nucleic acid vaccines—are DNA and mRNA vaccines. These vaccines involve the injection of the nucleic acids DNA and mRNA, respectively. Although both deal with different molecules, their mechanisms overlap, so it is necessary to understand how DNA and mRNA interact.

   DNA, which stands for deoxyribonucleic acid, is a long molecule that contains genetic information for making proteins. When the body needs to produce a particular protein—such as collagen—the DNA fragments that code for collagen are transcribed into another molecule called messenger RNA (mRNA). Afterward, the produced mRNA carries its information to ribosomes, which are the cells’ protein-manufacturing sites.

    Third-generation vaccines essentially take advantage of this two-step process of protein synthesis. The DNA and mRNA vaccines insert the instructions to make COVID-19 protein antigens into our cells in the form of DNA or mRNA molecules. As a result, our cells gain the ability to make immunogenic particles. These resulting protein particles are then attached to major histocompatibility complexes (MHC)[6], which act like bulletin boards that display the body’s new targets to immune cells called lymphocytes, triggering an adaptive immune response against them.

   The AstraZeneca and Janssen COVID-19 vaccines—both DNA vaccines—contain DNA that codes for a specific protein found on the surface of SARS-CoV-2, the virus that causes COVID-19. However, the spike DNA is not directly injected. It is first enclosed in adenoviruses that carry the spike DNA into our human cells as if they were infecting the human body. Since these adenoviruses are modified, they cannot cause disease and only deliver vaccine DNA[7][8].

   Although mRNA vaccines from Moderna and Pfizer-BioNTech are considered newer than DNA vaccines, they utilize similar mechanisms. Rather than inserting DNA, mRNA vaccines deliver mRNA and transport them in lipid (fat) nanoparticles—not adenoviruses—that can cross the cell barrier and reach the ribosomes. Also, unlike DNA vaccines, mRNA vaccines only go through one stage of protein synthesis [9][10].

Cautious optimism

  Third-generation vaccines, particularly mRNA vaccines, bring countless possibilities to the vaccine industry. Moderna’s and Pfizer-BioNTech’s vaccines are the first mRNA vaccines to have been released for use and are also the most effective. Both vaccines have shown efficacy rates of 95%, which compare to the 65% and 70% rates of the Janssen and AstraZeneca DNA vaccines, respectively[11].

  Nevertheless, the development of mRNA and DNA vaccine technology understandably comes with unease. One of the main concerns is the side effects. While they do occur, the side effects are similar to those of other types of vaccines. For instance, pain at the injection site and cold-like symptoms are common following vaccination. The latter is actually a positive indication that our immune system is building a defense against the virus particle. However, it is possible for side effects that were not anticipated by clinical trials to appear, so researchers are closely monitoring vaccination programs[12].

   But what about the long-term effects of getting vaccinated? Simply put, there is no way to determine the long-term effects because the vaccines have not been released for long enough. However, based on what is known about the safety of the vaccines, there is “nothing […] that suggests any risk or reason for long-term side effects[13].” Regardless, scientists will continue to monitor the vaccinated population over and the next few years. While vaccination is ultimately an individual’s choice, the immediate threats and risks of COVID-19 make vaccines a favorable option for many.

   There are also rumors that these vaccines can alter our DNA, but experts have quickly dismissed these claims as “myths[14].” As previously described, mRNA molecules are entirely different from DNA and are also more unstable, so they degrade before having the chance to enter a cell’s nucleus, where DNA is stored. But DNA vaccines, on the other hand, do enter the cell nuclei. While there was initial worry over vaccine DNA integrating with our DNA in the nucleus, Professor Ha Sang-jun (Prof., Dept. of Biochemistry) claims that “the chances of this occurring are considerably low,” given the fact that all approved vaccines have gone through rigorous testing during clinical trials.

   The short development timeframe is yet another concern. However, the shorter timeframe does not mean that clinical trials were omitted or skipped. The time compression can be attributed to the fact that it is easier to make DNA and mRNA vaccines for a new pathogen by manipulating the inserted genetic code. Likewise, the adaptability of third-generation vaccines is likely to help the world prepare for future outbreaks of new COVID-19 variants and even entirely new pathogens[15].

   More importantly, the hope that third-generation vaccines bring extends beyond infectious diseases and pandemics. “mRNA vaccine technology is promising,” says Professor Ha. “These vaccines have high efficacy rates and are more precise in terms of targeting and expression of proteins.” Moreover, given the versatility of mRNA vaccines, Professor Ha highlights their applicability for a broader range of diseases, including cancer. “Cancers require immediate, short-term treatment. Since mRNA vaccines are directly translated into proteins, they are an optimal platform for treatment development.”

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   New scientific developments, such as mRNA vaccines in the pharmaceutical industry, can be both exciting and worrisome. However, by understanding the nature and potential of these vaccines, we can make more informed choices and overcome skepticism in the face of new, promising advances.

[1] Pathogens: Microbes that cause disease

[2] Antigens: Particles usually found on the surface of pathogens that antibodies can bind.

[3] Campbell Biology

[4] Journal of Archives in Military Medicine

[5] Current Tropical Medicine Reports

[6] MHC: Protein complexes found in all cells

[7] AstraZeneca

[8] Janssen

[9] Moderna

[10] Pfizer

[11] BioSpace

[12] Horizon

[13] Houston Methodist Hospital

[14] Reuters

[15] CDC