COVID-19: Efficacy review of Moderna vaccine

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Yesterday I reviewed the safety of the Moderna vaccine. Today I’ll review the effectiveness of the vaccine, provide a bit of information on prevention of asymptomatic infection, as well as effectiveness after only one dose and give you my conclusions. I will follow the same template I did for my review of the effectiveness of the Pfizer vaccine in order to give as much of an apples to apples comparison as possible.

Please refer to my post on the effectiveness of the Pfizer vaccine to get key definitions, a discussion of confidence intervals, and preventing infection versus disease. 

A note on the new COVID-19 strain in the UK

The UK reported that there is a new strain of COVID-19 with increased contagiousness. After reviewing some more in-depth news reports, however, there is some debate within the scientific community as to the clinical significance of this “new” strain. Early data is often very messy and sometimes downright incorrect. It is very difficult in the absence of large epidemiologic data sets to draw any conclusions as to whether the new strain is more contagious or virulent. And maybe increased contagiousness is less due to the virus but more to human behavior? 

Will this new mutation be able to “escape” the immune response created by the new vaccines? I don’t know, but I remain hopeful. Remember these important points:

1. There has been no reliable data put forth to support such a concern.
2. All RNA viruses mutate frequently, and COVID-19 is no different. The question is whether these mutations affect the ability of COVID-19 to elude the immune response generated by the vaccines. Measles virus is a RNA virus that mutates frequently but that hasn’t changed vaccine effectiveness. And influenza virus is a totally different animal — a seasonal virus with multiple different immune targets that regularly change over the course of days and weeks. 
3. Remember, COVID-19 is absolutely dependent on the spike protein to bind with the ACE-2 receptor, infect people, and continue its lifecycle. Any genetic mutation in that spike protein has to keep the underlying functionality intact. That may be a very narrow genetic needle to thread. 
4. Early immunogenicity data from the mRNA vaccines demonstrate an immune response to multiple parts of the spike protein as well as the major genetic variants to date.

I’ll get concerned about COVID-19 eluding the vaccine immune response when there is good data corroborated by multiple sources to support that concern.

How effective is the Moderna vaccine? And how confident are we of these numbers?

Now that I’ve had the chance to look at the data I can say the following: the Moderna COVID-19 vaccine is extraordinarily effective at preventing COVID-19 disease, and I am extremely confident in that statement. You’ve already seen the top-line number that the Moderna vaccine is 94.1% effective in preventing COVID-19 disease. Of equal significance is that the confidence interval is narrow, between 89.3% and 96.8%. These numbers are very similar to those with the Pfizer vaccine. Although we cannot directly compare the vaccines without an additional clinical trial, there is no reason to conclude anything but these vaccines are equally effective.

As with the Pfizer vaccine, the Moderna vaccine had very similar effectiveness in all the major subpopulations in the clinical trial. In other words, the vaccine was uniformly effective in younger patients, older patients, patients with high-risk medical conditions and those without, different racial and ethnic groups — essentially every group we are interested in.

A note on effectiveness between dose 1 and dose 2

Both Pfizer and Moderna included data that showed a lower rate of COVID-19 disease in patients who had received dose one but had not yet received dose two of the vaccine compared to those who were between dose one and dose two of placebo. But the studies were not designed to measure this outcome, and nearly all recipients ended up getting two doses anyway. If you want to say for certain that these vaccines prevent disease after only one dose then you have to design a study that evaluates only one dose. That study won’t happen of course. So we have to make reasonable conclusions based on the available information. Both vaccines showed a rather remarkable divergence in rates of COVID-19 disease between placebo and vaccine recipients starting about 14 days after the first dose. 

Here is my conclusion: both vaccines provide some effectiveness after dose one but we have insufficient information to provide a reliable estimate of this effectiveness. In addition, based on what we know of vaccines and immunology, reliable, predictable, and durable vaccine responses require a booster dose. Therefore, feel good about starting the vaccine series, but don’t feel protected until somewhere between seven and 14 days after the second dose. 

How effective is the Moderna vaccine in preventing severe disease?

The number of patients who progressed to severe COVID-19 disease were very small, so we cannot say for certain that the Moderna vaccine prevents severe disease. That being said, there were 30 cases of severe disease in patients who received placebo and zero cases of severe disease in patients who received the vaccine. I think both the Pfizer and the Moderna vaccines will be shown over the long-term to be extraordinarily effective in preventing severe COVID-19 disease. That being said, I am a husband so all my claims need to be taken with a large grain of salt. 

Can’t you give us any information about prevention of infection?

Moderna tested their study population for asymptomatic infection (they collected PCR swabs in patients who did not have symptoms of illness) prior to the first and second doses of vaccine or placebo. The numbers are small but important. In the vaccine group 0.1% (14 / 14,134) had asymptomatic infection prior to dose two vs. 0.3% (38 / 14,703) in the placebo group. The most scientifically accurate statement we can make is that the rate of asymptomatic infection was about two-thirds lower in vaccine versus placebo recipients. We cannot say that the vaccine caused this reduction because of the small numbers, the design of the study, etc. As I stated in this post, I will be surprised if these first two vaccines do not prevent infection to at least some degree, but I am not going to make a prediction as to an exact percentage. 

I find this preliminary data encouraging. We will see more data released from these two studies, as well as from “real-world” data that will help answer this important question about preventing infection.

A note on immunology and duration of protection

Moderna released data similar to that from Pfizer regarding the immunogenicity of its vaccine. As with Pfizer, the Moderna vaccine produced uniformly high concentrations of neutralizing antibodies, there was a “boosted” response after the second dose, and the vaccine elicited a robust response of type 1 T-helper cells and all the various immune molecules (fancy things called interleukins and interferons) we want to see. 

In simple English, all the immunologic data currently available holds the very real promise of long-term protection. This does not guarantee long-term protection, but such protection wouldn’t even be a possibility if the data were otherwise. 

Both the Moderna and Pfizer vaccines encode for the same spike protein target so I would be surprised if there were any substantive immunologic differences between these vaccines.

What are my final conclusions and what would I do?

You can read my previous blog post to find my conclusion of the Pfizer vaccine. The Moderna vaccine has one significant practical advantage. It can be stored at normal freezing temperatures during transportation, and at the clinic, it can be stored at normal refrigerated temperatures for 30 days and up to 12 hours at room temperature. The vaccine also does not require any mixing after freezing, unlike the Pfizer vaccine. After first use the Moderna vaccine must be used within six hours, similar to the Pfizer vaccine which is good for only six hours after mixing. These advantages are real and substantial. If there were sufficient supply right now, I would happily receive the Moderna COVID-19 vaccine and would recommend it for my family, my aunt, my uncle, and my in-laws. If my mom and dad were alive right now, I would recommend it for them. 

Which vaccine would I prefer? 

Whichever one I can get first.

We’re getting there, we’re getting there.

Stay safe, and go make some lemonade.

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