Moderna CEO on mutations, mRNA vaccine side effects & efficacy, timeline to normalcy...

mRNA technology gives the same kind of antibody to 25 vs. 75-year-olds; new UK virus strain not more deadly and won't impact vaccine efficacy; recent suspension of Moderna vaccine in CA is no big deal

Jan 22, 2021

I sat in on a presentation by Moderna CEO Stéphane Bancel, who gave a comprehensive overview about the Moderna mRNA vaccine development process and addressed concerns related to efficacy rate, side effects, mutations, etc. Here are the punchlines. For more details about data and charts related to the points below, please feel free to contact me.

Overview of the Covid vaccine race

There are three kinds of Covid vaccines in the race:

mRNA vaccines, led by Moderna, BioNTech/Pfizer;
Vector vaccines, led by Oxford, Johnson & Johnson, Merck;
Protein vaccines, led by Chinese drug companies such as SinoPharm and Sinovac. So far no protein vaccine has been approved by the US authorities yet. It’s non-digital (unlike the vector & mRNA vaccines) so it takes much longer to develop and manufacture.

It took Moderna (and other big pharma companies) around 6-9 months to build a meaningful capacity for Covid vaccine production. They all invested a lot of capital over the last few months into R&D and manufacturing. The capital spent in this specific area went up 10,000x in the last year, which is impossible in any other industry if you think about it.

No other country has done as well as the U.S. to “build a portfolio.” Back in March nobody knew which technology was gonna work, and the U.S. government bet on all three kinds of vaccine technologies and really helped all 6 Western companies in the race with funding. The U.S. government was really helpful and instrumental in leading to the success and quick rollout of vaccines.

mRNA technology

The mRNA technology is wonderful. The error bar in terms of the efficacy for developing antibody is small. The nature of the mRNA technology means that someone who is 75-years-old would develop the same antibodies as 25-year-olds.

This was a whole new endeavor as Moderna previously had zero approved product in mRNA technology; very soon there should be a few dozens of drugs and treatments in the pipeline.

Vaccine efficacy

This is how the initial efficacy rate was calculated:

Total trial participants: 30,000
Infections in the vaccine group: 11
Infections in the placebo group: 185
Efficacy = (185-11)/185 = ~94%

The good thing about doing the trial in America is there were so many cases so Moderna got the data back very quickly. (To read more about how the Covid vaccine trials were conducted and why you should be very optimistic about these efficacy numbers, see my earlier email here).

Of all the people that got sick in the vaccine group, nobody died, was hospitalized, suffered severe side effects, etc. The worst someone got was no worse than typical post-flu-shot symptoms such as a fever. So, even if the Covid vaccines don’t work on you, it wouldn’t make you sick.

What’s the level of antibody that the mRNA vaccine can produce?

The medical community doesn’t yet know how much antibody you need in order to get fully protected from Covid. We also can’t measure/predict how much antibody you would get after the vaccine since you may have co-morbidity factors like obesity that bring down the antibody level. But you will get some antibodies at least, so we know that you won’t get severe reactions.

We also still don’t know enough about the infectiousness of the vaccinated people. They could still infect others even after developing antibodies themselves.

Should we worry about mutations?

Covid is an mRNA-based virus, so it’s much less stable. There have been mutations since last January, and scientists have been observing them very closely; it’s just only recently did the media start to report on them more widely to the public.

So far the mutations are within the bands of similarities of the original virus, so not a big deal so far. But if the pandemic goes on for longer, the new mutations might jump to be much different.

The new “UK strain” that’s been widely reported and all the other mutations documented so far are NOT more pathogenic/fatal. They’re more infectious, so more people will die, but they’re not more fatal.

How do the mutations affect vaccine efficacy?

Some mutations would impact the efficacy of the vaccines; some not.

According to CDC, this is how an mRNA vaccine works:

COVID-19 mRNA vaccines give instructions for our cells to make a harmless piece of what is called the “spike protein.” The spike protein is found on the surface of the virus that causes COVID-19.
Once the instructions (mRNA) are inside the immune cells, the cells use them to make the protein piece. After the protein piece is made, the cell breaks down the instructions and gets rid of them.
Next, the cell displays the protein piece on its surface. Our immune systems recognize that the protein doesn’t belong there and begin building an immune response and making antibodies, like what happens in natural infection against COVID-19.

In short, the vaccine allows your body to make antibody against a harmless spike protein. The spike protein is very long and big (4kb in length), and it has many nodes. The vaccine will result in antibodies for each of the node, and because the protein is so long, the antibodies will bind with so many different nodes of the spike protein such that even if one of the nodes have already mutated, there will be enough antibodies for all the rest of the nodes such that the vaccine will still be just as effective. Therefore, the new UK strain has little impact on the vaccine’s efficacy.

Does that make sense? Again, I’m not a science guy so if any of my understanding below is incorrect, please point it out to me and I’ll issue a correction. But here’s the rough explanation why the mutations aren’t a big deal.

Vaccine side effects?

Most side effects are very benign just like after normal flu shots – fever, not feeling well for a couple days, etc. These benign reactions are actually good because it means your immune system is getting activated.

Sure, when you vaccinate tens of millions of people, some people will have unknown side effects that weren’t previously discovered in the controlled trials. But the risk-reward that authorities have to weigh is different from individual considerations, and the risk overall is very low, while the benefit of mass vaccination is very high. The side effects shouldn’t deter us from pushing for mass vaccination.

But what about the more severe allergies?

If you have no history of allergies, you won’t get any allergies from this vaccine.

Recently, California suspended one of the batches of the Moderna vaccines after seeing severe allergic reactions. This incident raised concerns. What went wrong? Should that cause any alert? That clinical lot was put on hold. Moderna investigated and published the results:

All Moderna’s vaccines are given to the CDC and FDA; Moderna itself doesn’t ship the vaccines. That same clinical lot of vaccines were also used in more than 37 states without issue.
Moderna rechecked quality control criteria for that lot during the manufacturing process, and everything was fine there as well.

Some hypotheses: Was there a break in the cold chain that damaged the product? Was the preparation of the product done incorrectly in the pharmacy before administered? The investigation is still ongoing. But we know nothing was wrong with the actual vaccine or manufacturing process. Nothing to really worry about.

Long-term side effects of Covid?

Covid might cause some of your cells to merge and thus result in a loss of DNA. DNA is required to produce proteins, so the loss of DNA could result in heart tissues dying or lung scarring. Other side effects seen so far include:

Blood clots
Neurological problems (dizziness, headache, nerve pain, impaired consciousness)
Long-term fatigue and breathlessness

That’s why many doctors who read medical journals every day are really scared of the virus and still don’t go outside. The chances of such long-term effects are very, very low, though.

By the way, Covid is 10-20x more deadly than flu. That’s just a fact that deserves repeating.

Mass vaccination outlook and timeline for returning to normalcy?

The current data shows a 60% efficacy rate after first dose. Hopefully the ratio will be much higher after the second dose has been widely administered. We will get data by March.

If we get to March and April, and 20-25% of the U.S. population are vaccinated (which include the most vulnerable populations like 70+-year-olds and the super-spreader populations like prison and nursing homes), we’ll have a disproportionate benefit to the economy.

Then, the infection number will still be high, but the mortality and hospitalization numbers will become much lower. That will be a good outcome.

By the end of Q2, most above 18 who want a vaccine should have been vaccinated.

CDC indicates that there have already been 20 million documented infections; we also suspect that 50-60 million may have been infected but not officially documented. So the path to herd immunity is optimistic by the end of Q2.

As always, please let me know your thoughts. You may leave a public comment, or privately respond to this email which will carry your words directly to my personal inbox.

Tiger Gao & Policy Punchline

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