Moderna Vs. Pfizer mRNA Vaccines for Covid-19: The Key Points
By: Shin Jie Yong
Tags: Technology, Science, Innovation, Coronavirus, Life

Moderna Vs. Pfizer mRNA Vaccines for Covid-19: The Key Points

Explaining the efficacy and safety profiles, handling protocols, and remaining questions about disease spread and long-term immunity and safety between the two vaccines.

Photo by Nataliya Vaitkevich from Pexels

The fastest vaccine the FDA has approved was the Ebola DNA-based vaccine that took about five years. For Covid-19, in less than a year, we already have two candidate vaccines — mRNA-based vaccines from Pfizer and Moderna — awaiting approval this year or early 2021. A record-breaking indeed. How do the two mRNA vaccines compare, and what makes them so effective? And what are the things left unanswered?

Current knowledge

1. Efficacy

While data is yet to be published as formal peer-reviewed scientific papers, Pfizer claimed a 95% efficacy, and Moderna claimed a 94.5% efficacy in preventing Covid-19 infections in press-releases. As Pfizer has not provided as much clinical information as Moderna, this section will focus on the latter.

As it’s our own cells that make it, the protein’s expression and levels are more stable and, thus, enable a more potent immunogenic response.

Moderna’s phase III clinical trial enrolled 30,000 participants in the U.S. and randomized them into the vaccine or placebo group. After administering the shots on day-1 and day-29, the researchers waited until 95 participants become positive for SARS-CoV-2.

(Assuming 1% of the population gets infected, we can expect 300 infections out of the 30,000 sample size, so 95 is a satisfactory number.)

The trial then unblinded the 95 participants. Results found that 90 of them belonged to the placebo group and only five to the vaccine group. In these 95 cases, there were 15 adults aged >65 and 20 people of color. Moderna’s trial also reported 11 severe Covid-19 cases that all belonged to the placebo group. This means that Moderna’s vaccine is 94.7% (90/95) effective in preventing Covid-19, which applies to severe cases and diverse populations.

19th November update: Pfizer just updated their webpage to provide more clinical information. Pfizer’s clinical trial recruited 43,000 participants with a similar study design as Moderna’s. Pfizer did the unblinding once they reached 170 cases of Covid-19, of whom 162 were in the placebo and eight in the vaccine group. There were 10 severe cases, of which nine belonged to the placebo group. The vaccine was also effective across age, sex, race, and ethnicity groups. Overall, that makes 95.3% (162/170) effectiveness.

The striking effectiveness of the mRNA vaccine lies in its biology. mRNA stands for messenger RNA, a genetic sequence that carries information that the cell’s ribosome reads. mRNA thus messages the cell’s ribosome to make new proteins without any involvement of outside proteins or microbes (as seen with traditional vaccine types). As it’s our own cells that make it, the protein’s expression and levels are more stable and, thus, enable a more potent immunogenic response.

2. Safety

Both Pfizer and Moderna reported no significant safety concerns about their vaccines. While Pfizer has not released the specifics data about its vaccine’s safety, Moderna has documented a few.

In Moderna’s clinical trial, side effects include fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%), and redness at the injection site (2.0%) that are temporary. These side effects are also commonly seen with other vaccines, so they are not much of a concern.

19th November update: Pfizer’s clinical trial reported that notable side effects with over 2% occurrence were only fatigue (3.8%) and headache (2%). These lesser side effect rates than Moderna’s is an encouraging finding.

But considering that mRNA is so fragile, long-term health problems are unlikely.

3. Storage conditions

Pfizer’s vaccine needs to be stored at -70°C or below. In contrast, Moderna’s vaccine only requires a -20°C storage condition, the same as a regular fridge freezer. Both vaccines can last for six months in their respective temperatures. Moderna’s vaccine can even be stored at 2–8°C for 30 days, and at room temperature for 12 hours. So, Moderna’s vaccine is much easier to distribute.

As mRNA is single-stranded, it’s much less stable than its DNA counterpart and degrades easily. So, a freezing temperature at -70°C preserves the mRNA integrity. In contrast, DNA is double-stranded and coiled into a helical formation that is more structurally tough.

But Moderna’s vaccine used a lipid nanoparticle coating to increase the mRNA stability. “[It’s] kind of like putting your chocolate inside a candy coating — you have an M&M, so the chocolate doesn’t melt,” explained Margaret A. Liu, professor of microbiology and immunology at the University of California and a former president of the International Society for Vaccines. As expected from a company that developed two candidate mRNA vaccines in the past, this is very innovative.

4. Booster shots

Pfizer’s vaccine requires two shots taken three weeks apart (i.e., days 1 and 22). The same applies to Moderna’vaccine that needs two shots taken four weeks apart (i.e., days 1 and 29). This means double the syringes, clinical visits, vaccine vials, time, and workload.

For Pfizer’s vaccine, it also means twice the trouble in distributions, owing to its strict storage condition, especially in developing countries or areas. For Moderna’s vaccine, the one-week extra time between shots is also encouraging as it allows a buffer time for any unexpected events.

Remaining questions

1. Transmission

For one, we still don’t know if these vaccines prevent transmission. “Even if [Covid-19] vaccines were able to confer protection from disease, they might not reduce transmission similarly,” a paper in The Lancet stated.

However, if the vaccines protect the high-risk groups, that alone would significantly reduce the pandemic’s health burden. As one in five SARS-CoV-2 infections shows no symptoms but remains contagious, we should hope that the mRNA vaccines stop transmission as well.

Plus, we can control a few lifestyle factors to maximize our chances of successful, potent immunization.

2. Long-term efficacy

As these mRNA vaccines rely on B-cell antibody responses that tend to wane over time, lifelong protection is not guaranteed. But the good news is that these mRNA vaccines also trigger T-cell immunity, although to a lesser extent than B-cell, which could provide a more robust immunological memory. Another upside is that even waning antibodies can still provide protection via other mechanisms such as T-cell-induced activation of antibodies.

So, we can be assured that immunity does not fade easily. Immunity may be less effective but unlikely to turn zero. Plus, we can control a few lifestyle factors to maximize our chances of successful, potent immunization.

3. Long-term safety

This one is controversial. As mRNA vaccines are new inventions, they have never been approved for any infectious diseases. So, there are no prior research or historical records we can rely on, unlike the traditional types like live, inactivated, or protein-based vaccines. But considering that mRNA is so fragile, long-term health problems are unlikely.

“We will have a safety profile for only a certain number of months, so if there is a long-term effect after two years, we cannot know,” said Dr. Tal Brosh, head of the Infectious Disease Unit at Samson Assuta Ashdod Hospital. If we wait for two years, “then we would have the coronavirus for two more years.”

Short abstract

Moderna’s vaccine has less stringent storage and booster shot requirements, which helps make mass distribution easier. Both Moderna’s and Pfizer’s vaccines have similar efficacy at around 95%, which applies to severe Covid-19 cases and diverse populations with no major safety issues. Notably, Pfizer’s vaccine has lower side effect rates than Moderna’s. But whether these mRNA vaccines stop transmission, provide lifelong immunity, or are safe in the long-run remains unanswered.

Still, mRNA vaccines' success is something to be optimistic about as it’s one step closer to normalcy. Lastly, comparing the two mRNA vaccines shouldn't promote competition as “this really isn’t a race,” said Professor Liu. “Just by sheer numbers, we probably need multiple, multiple vaccines.” Who knows if the third vaccine (like AstraZeneca’s one) is the better one.

December 2020 updates: Both Moderna’s and Pfizer’s mRNA vaccines for Covid-19 have successfully attained FDA approval for public use.