Pfizer's COVID-19 Vaccine: The World's First mRNA-based Vaccine

It’s been about a year since I first wrote “Crash Course on COVID-19”. When writing that article, it was difficult to separate fact from speculation simply due to the novel nature of the SARS-CoV-2 virus. It required a constant revision of case totals, mortality statistics, and information concerning the pathogenicity of the virus. In fact, scientists could not even be certain whether SARS-CoV-2 could be transmitted asymptomatically, something considered layman’s knowledge today. From confronting the first case of COVID-19 to sifting through the seas of uncertainty regarding the mechanisms of its behavior, we have generated a sound vaccine within a span of 12 months, pooling the brightest minds and financial resources from all over the world. It’s an achievement of unprecedented magnitude that set a new standard for global health.

On December 11, 2020, the U.S FDA issued the first emergency use authorization for a vaccine, allowing the Pfizer-BioNTech COVID-19 Vaccine to be distributed (Office of the Commissioner, 2021). Operating as a two-dose vaccine, each shot in the upper arm muscle is given 21 days apart. What makes the Pfizer vaccine interesting to note is the fact that it is an mRNA-based vaccine, a new approach to protect against infectious diseases. 

In any virus, its antigens are the surface proteins characteristic to what makes that virus uniquely dangerous. Typically, vaccines work by injecting a weakened, less dangerous form of the antigen such that our immune system can generate a proper immune response via antibodies. The annual influenza vaccines we receive during the fall operates like this. On the other hand, mRNA vaccines inject a messenger RNA that essentially serves as an instruction manual for our body to produce the antigens themselves (Centers for Disease Control and Prevention, 2021). Specifically, the mRNA from Pfizer encodes a key domain of the spike protein found on SARS-CoV-2 that enables it to be dangerous in the first place (Sahin et al., 2020). Our body subsequently “presents” the antigens to coordinate with our immune cells in an effort to promote antibody response. Thus, instead of facing a weakened form of the virus, our bodies are manufacturing the signature protein of the virus. 

However, we can’t just inject mRNA into the body; humans, thankfully, do have plenty of safeguarding mechanisms to destroy foreign substances through our natural enzymes circulating the body. In order to circumvent this preemptive destruction , Pfizer developed an mRNA vaccine technology to allow delivery of the genetic information by enclosing the mRNA in a lipid nanoparticle. These nanoparticles can fuse with the body’s cells to release the mRNA into them, as shown in the picture below (Corum & Zimmer, 2021). The protein-building machinery in our cells reads the mRNA to build the aforementioned spike proteins, which stick out like projections on the surface of our cells, where they wait for our immune cells to notice them. Eventually, the body will be able to form immune cells called memory cells that recognize the spike protein, functioning as a potent neutralizer for future infections. A two-dose system is required because the first dose primes the immune system, offering protection for about 10 days with a 52% effectiveness. The second dose results in sustained protection with a 95% efficacy rate, as determined by Pfizer’s clinical trials (Corum & Zimmer, 2021). However, it is not yet known how long the protection will last. 

Figure 1. Liposome-mediated entry of Pfizer’s novel vaccine nanoparticles (Corum & Zimmer, 2021)

The vaccine’s main purpose is to prevent individuals from succumbing to the virus. A study from Israel conducted the largest real-world study of Pfizer’s vaccine to date, which reveals that the vaccine is 98.9% effective at preventing deaths and 99.2% effective at preventing serious disease (Bowden, 2021). These numbers are staggering, given that more than 165 million doses have been doled out in the U.S. alone. It should be noted, however, that the concept of a vaccine is not to prevent transmission, though that may be a fortunate byproduct. Preliminary data has shown both Pfizer and Moderna vaccines to significantly reduce transmission, but there is still no conclusive evidence of this. Transmission in this sense refers to the chance of a vaccinated individual developing an infection and passing it along (Piper, 2021). This means even though we’ll have massive vaccine rollout in the coming months, wearing a mask will still be required until a passable level of herd immunity has been reached or irrefutable evidence from Pfizer demonstrates a reduction of transmission. 

Pfizer’s vaccine is known to produce a host of undesirable side effects, including headaches, fever, nausea, chills, etc. Unfair criticism has been directed towards the vaccine by uneducated individuals because of this without realizing that these are simply signs of the immune system at work attempting to build immunity. In other words, this has caused many people to misguidedly question the safety of the vaccine, even though such side effects are normal and are to be expected. For example, our body will raise its internal temperature to make the living conditions of the pathogen unbearable, allowing for our immune system to produce a robust response against the virus. Consequently, we perceive the outward symptoms as a fever. 

The bottom line is that there’s an insurmountable amount of evidence validating the work of Pfizer’s new mRNA-based nanoparticle technology. Administering mRNA as opposed to antigens typically used in previous vaccines can shave off months in the production process due to how quickly we’re capable of making it. This is due to mRNA being a stranded piece of information rather than a complex folded protein, which explains why such technology holds so much promise for the future of vaccine technologies (Stanley-Becker, 2021).

There is talk of utilizing and applying this mechanism to the influenza vaccine (Stanley-Becker, 2021). Since every year a new influenza vaccine must be developed to account for new strains in the population, it would be extremely useful to test an mRNA-based vaccine given the high mutation rates of influenza. All signs indicate that it is much easier to modify an RNA vaccine (Stanley-Becker, 2021). 

The challenge of vaccine distribution still remains pervasive. There has been a slower-than-anticipated rollout to aid individuals with comorbidities due to Pfizer, Moderna, and Johnson & Johnson being the only American pharmaceutical companies who have FDA-approved vaccines. It’s a tall task for them to reach their target goal of 220 million shots by the end of March (Stanley-Becker, 2021). The possibility of Johnson & Johnson among other companies joining the fray with their own vaccines can potentially speed up the process. Nonetheless, the progress towards reaching the threshold for herd immunity at a 70-80% vaccination rate of the entire U.S. population will take time, with President Biden hoping to vaccinate every adult by the end of May. 

References

Bowden, J. (2021, February 21). Israel: Pfizer vaccine prevents 98.9 percent of COVID-19 deaths. The Hill. https://thehill.com/policy/healthcare/public-global-health/539778-israel-pfizer-vaccine-prevents-989-percent-of-covid-19

Centers for Disease Control and Prevention. (2020, February 11). Understanding How COVID-19 Vaccines Work. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html

Corum, J., & Zimmer, C. (2021, February 24). How the Pfizer-BioNTech Covid-19 Vaccine Works. The New York Times. https://www.nytimes.com/interactive/2020/health/pfizer-biontech-covid-19-vaccine.html?auth=login-google1tap&login=google1tap

Office of the Commissioner. (2021, February 3). Pfizer-BioNTech COVID-19 Vaccine. U.S. Food and Drug Administration. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine

Piper, K. (2021, February 23). Covid-19 vaccines: the growing evidence they can reduce transmission. Vox. https://www.vox.com/future-perfect/22291959/covid-vaccines-transmission-protect-spread-virus-moderna-pfizer

Sahin, U., Muik, A., Derhovanessian, E. et al. (2020). COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature, 586(7830), 594–599. https://doi.org/10.1038/s41586-020-2814-7

Stanley-Becker, I. C. R. (2021, February 23). Vaccine makers Pfizer and Moderna pledge massive boost to U.S. supply after sluggish rollout. Washington Post. https://www.washingtonpost.com/health/2021/02/23/vaccine-distribution-pfizer-moderna/