Pfizer and Moderna vaccines for COVID-19 – differences and similarities

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If you are an American, you probably could not avoid noticing the news that the Pfizer and Moderna vaccines for COVID-19 have shown >90% effectiveness in preventing the disease over the short-term. And both companies would probably be seeking an Emergency Use Authorization (EUA) in the USA for use of their vaccines in groups who are most in need of protection from COVID-19. 

Even though I’ve discussed the positive and negative points about the Pfizer and Moderna COVID-19 vaccines, I think it’s important to highlight the similarities and differences between the two vaccines. Also, please note that these vaccines probably will be released first in the USA, especially Moderna who received support from the Federal Government through Operation Warp Speed (Pfizer opted out of it). There are several other vaccines in phase 3 clinical trials that could be seeking a EUA sometime in the near future in the USA and Europe. 

COVID-19 vaccine candidates in phase 3 clinical trials – the official list

Moreover, there are over 200 COVID-19 vaccine candidates in development, with dozens in phase 1 and phase 2 clinical trials. By early 2022, we could be comparing 10 or 15 vaccines that might be entering the market. 

But this article is just going to focus on the Pfizer and Moderna COVID-19 vaccines. I’m going to hit the key similarities and differences between the two vaccines. I may conclude with my opinion on which one will be successful, but we might not know for years which of all of these vaccines are the “best.”

Pfizer and Moderna vaccines technology

Both the Pfizer and Moderna vaccines employ an mRNA vaccine technology that has come to the forefront of vaccine research and development.

These mRNA vaccines rely upon an mRNA, or messenger RNA, molecule to induce an immune response. Normally, mRNA molecules in the cell correspond to DNA sequences in genes and carry that information to be “read” by a ribosome to produce a protein. 

Alan McHughen, in “DNA Demystified: Unraveling the Double Helix,” describes how mRNA works:

When an mRNA strand exits the nucleus and enters the cytoplasm, it attaches to ribosomes, and this is where protein synthesis progresses. The ribosome reads the base sequence of the mRNA, three bases at a time. Each three-base triplet, called a codon, specifies a particular amino acid, except for a few with regulatory functions (e.g., UGA =“Stop!”).

If the first three-base codon is AUG, then a molecule of the amino acid methionine is brought into place. If the next triplet is AAA, that brings in the amino acid lysine. The methionine and lysine molecules are attached together. The next triplet is, say, GCC, and that brings in alanine, which is attached to the lysine. The ribosome has read nine bases, AUGAAAGCC, and compiled a short chain of three amino acids, abbreviated Met-Lys-Ala, or MKA (see amino acid abbreviations here).

The ribosome continues reading all of the mRNA bases until it hits a stop signal—which is also a triplet codon such as UGA—and the now long chain of amino acids falls loose. This chain may be a functional protein immediately, or, more usually, it might undergo some additional post-translational processing by enzymes to become active.

Moderna and Pfizer mRNA vaccine technology relies upon a specific mRNA to kickstart the endogenous production of proteins that are similar to some of the SARS-CoV-2 antigens, specifically the S-protein or spike that iconic on every image of the virus. These antigens produced by our own cells will trigger the body’s adaptive immune system to produce antibodies effective against the actual target, the SARS-CoV-2 virus.

3D print of a spike protein on the surface of SARS-CoV-2—also known as 2019-nCoV, the virus that causes COVID-19. Spike proteins cover the surface of SARS-CoV-2 and enable the virus to enter and infect human cells. For more information, visit the NIH 3D Print Exchange at 3dprint.nih.gov. Credit: NIH.

In other words, instead of injecting a live-attenuated vaccine, like the measles vaccine which contains weakened measles virus, the Pfizer and Moderna COVID-19 vaccines inject mRNA fragments that are selectively delivered to cells to produce the viral antigens (but not the whole virus, of course).

Despite the claims of some really outlandish pseudoscience in the anti-vaccine world, this mRNA vaccine will not “hijack” your DNA, self-replicate to turn you into a huge coronavirus, nor mutate into a new form of the virus. It is self-limiting because the mRNA molecule does not replicate and it is quickly destroyed after it produces the protein.

This mRNA vaccine technology is very new, Moderna has been working on them for years, never getting a vaccine past a phase 2 clinical trial (in a normal world of vaccine development, this just means everyone is taking their time). Because it is a new technology, I wish that we could take a much longer time to analyze it, but a single day’s delay in a vaccine could mean thousands of deaths.

You may be wondering why this mRNA technology has come to the forefront of the battle against COVID-19. There are two major theoretical advantages to this technology:

  1. mRNA vaccines may stimulate a more robust immune response because there might be a more specific response to these S-proteins.
  2. Manufacturing mRNA vaccines are less expensive and can be scaled-up faster than other types of vaccines.

Is that 90% effectiveness accurate?

Vaccine effectiveness is a statistical measurement that is based on data from clinical trials. It is a simple calculation that compares the risk of contracting the disease between vaccinated and unvaccinated groups. A 90% effectiveness implies that the vaccinated group has a 90% lower risk of contracting the disease.

But this number is not everything that we would like to know about any COVID-19 vaccine. We also would like to know whether the vaccine reduces the severity of the disease, whether it improves outcomes, or whether it has an effect on asymptomatic infections.

The latter concern is important because asymptomatic carriers could continue to spread the disease if the vaccine has no effect on them. It is unclear whether these vaccines are preventing asymptomatic infections. 

I would also like to see more robust data on the effectiveness of both vaccines with important subpopulations – seniors, people of color, lower-income individuals, and those with medical comorbidities like obesity, diabetes, and other conditions. Furthermore, we don’t have any data about the long-term effectiveness – does this vaccine prevent the disease for six weeks, six months, or six years.

Difference between Pfizer and Moderna vaccines

As I mentioned, the two vaccines are based on similar mRNA technology. There probably will be little difference between the vaccines in safety or effectiveness. Neither vaccine showed any important safety signals during their phase 3 clinical trials.

The most important difference between the Moderna and Pfizer vaccines is in the area of distribution and storage.

The Pfizer vaccine must be stored in a medical-grade deep freezer, at an average of -70ºC (or -94º in barbarian measurements). Those types of freezers are not generally in most medical facilities. And shipping the vaccines to outpatient offices and hospitals is going to be difficult since your standard UPS truck won’t have that type of refrigeration either. It will require dry ice (solid carbon dioxide) for shipping, which is a more difficult process.

On the other hand, the Moderna vaccine can be shipped at -20ºC (-4º barbarian) and can be stored up to 30 days in a standard refrigerator.  So, the Moderna vaccine will have an easier distribution system than the Pfizer one.

The reason why both require cold temperatures is that the mRNA molecule is an unstable molecule and can degrade quickly in warmer temperatures. Even the Moderna vaccine will be ineffective if it is kept at room temperature or warmer for even a few hours.

In addition, each of the vaccines will require two doses. The Moderna vaccine must be given 28 days apart, and the Pfizer vaccine must be given 21 days apart. This is one of my concerns about both of these vaccines because there might be a certain percentage of patients who will not get the second dose meaning they may not be completely protected against the disease.

So which vaccine is the best?

Although I remain concerned about the speed of this vaccine development process, especially if it becomes a political decision rather than a scientific one, and I would like to see more of the raw data from the clinical trials from both Pfizer and Moderna, I am cautiously optimistic about whether we get these vaccines. 

I am also optimistic that independent scientists will be reviewing the data before making recommendations. The CDC’s Advisory Committee on Immunization Practices, which makes recommendations on vaccines for children and adults in the USA, will be reviewing the current status of all of the coronavirus vaccines. 

Although I do not have access to the phase 3 clinical trial data, I am confident that vaccine scientists will have access to it and will make it clear whether they are concerned or happy. Assuming that both vaccines are safe and effective, the only major difference between the Pfizer and Moderna vaccines is logistics, and in that case, Moderna wins.

As long as Donald Trump or his sycophants are not unduly influencing the decision process for approving these vaccines, I am cautiously willing to get either of the vaccines. 

And I need to reiterate an important point. If either of the vaccines receives a EUA, it will be for specific groups of people, such as healthcare workers or those with significant comorbidities. Furthermore, the supply of the vaccine will be very low until probably mid-2021. 

This means that there will not be enough vaccine to get even close to a COVID-19 herd effect, so social distancing and masks are going to be your way of life for several more months, may even a year.



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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!