Which Vaccine?

If you’re a regular reader, you’ll be familiar with my general complaints about pandemic messaging. Put very broadly, I think the public health messaging is too eager to give definite answers when the evidence is still uncertain, and too willing to issue sometimes patronizing platitudes. This has come up again in the context of comparing across vaccines. The US has now approved three vaccines for COVID-19. The Pfizer and Moderna vaccines are very similar, and have been approved since December. The Johnson and Johnson vaccine (which I will refer to as J&J for short) was only recently approved and is beginning to be rolled out. The efficacy numbers in the trials of these vaccines differ; J&J is lower. More on what these numbers mean below, but if you look at the top line numbers quoted, this is what you see. At the same time, we are hearing “All the vaccines are awesome!” and “The best vaccines for you is the one you are offered.” This last line worries me especially since I think it runs the risk of suggesting that some people deserve to get a less good vaccine. So I’d like to dig into this a bit more deeply so we can understand better what we do know, what we don’t yet know, and how to think about the differences across these options. Before getting into this, I want to reiterate a point I’ve made before. These vaccines will not eliminate COVID-19, at least not for decades. They will also not prevent all cases of symptomatic or asymptomatic illness. They prevent a lot! But, not all. What is most impressive and most important about all of the vaccine options is that they do a great job preventing very serious illness. If we can get to a point where COVID-19 is relatively rare and where people who do get it experience mild symptoms, that will be winning. This is where we are aiming. Not zero COVID. What is the Difference between Vaccines? Let’s start with the question of what the difference is between the vaccines. Both the Pfizer/Moderna vaccines and the J&J work through the mechanism of delivering instructions to your cells to manufacture the COVID-19 spike protein. Your immune system then produces antibodies to recognize this spike protein and kill it. If the COVID-19 virus is then introduced to your body, you’re ready for it. The difference lies in how instructions are delivered. The Pfizer/Moderna vaccines deliver instructions through mRNA, and J&J delivers them through DNA embedded in another type of virus (an inactivated adenovirus which cannot make you sick). An advantage of the DNA delivery mechanism is that DNA is more stable than RNA, which is why the J&J vaccine can be stored at more normal temperatures. The difference in delivery mechanism opens up the possibility for differences in efficacy. These vaccines work better if they generate a stronger immune response, which will happen if the delivery mechanism is better able to get the virus into your cells. If you’ve already been exposed to the adenovirus used in the J&J vaccine it may work less well (because you’re immune to the delivery vector). On the other hand, the mRNA delivery mode in the Pfizer/Moderna vaccines is new, and it’s possible it works better for some people than others. Efficacy Numbers When we talk about efficacy of these vaccines, the first thing we want to run down is — based on what we see in trials — how good a job do the vaccines do at preventing various stages of illness. The vaccines are all extremely effective at preventing death. The J&J is slightly less effective in the trial data against serious illness and against symptomatic and asymptomatic illness. It is important to be clear on what these numbers mean. A 95% efficacy does not mean that 5% of people in the trial with the vaccine got symptomatic COVID! What it means is there was a 95% reduction in the risk from the baseline. If your baseline risk of getting serious COVID without the vaccine is, say, 1 in 100 then your risk with the Pfizer or Moderna vaccine is 1 in 2000. With the J&J it would be 1 in 666. These numbers are all extremely high. Flu vaccines, by contrast, often have efficacy numbers against symptomatic illness that are under 50%. It’s still very useful to have them, but they pale in comparison to any of these options. Based on the simple table above, it does look like the J&J performs slightly less well. However, we cannot directly conclude this because these were not tested in head to head trials. The conditions under which they were evaluated differed in a number of ways, the most important of which is that the J&J was tested in a period with more variant activity. All of the vaccines are likely to be at least slightly less effective against variants, so this could drive some of the differences (put differently: the Pfizer/Moderna numbers could be a bit lower in the variant space, or the J&J numbers could be higher without the variants). In addition, although these trials are enormous, there is still statistical noise — error — in their estimates. The data in all trials are consistent with a range of values, so point estimates do not tell the whole story. To really figure out which is “better” (if one is) we’d need to test them head to head in a trial. We might eventually get that, but there isn’t much point at the moment given that all are preforming well. Bottom line: based on my read of the data and many conversations with people who know a lot of stuff I don’t, I think the J&J is likely to be slightly less effective against symptomatic illness than the others, although I think the differences are smaller than the numbers above. (What if you’re pregnant or breastfeeding? Basically same deal across all vaccines: they’re not yet formally tested but there is no reason to think they are a problem and getting COVID in pregnancy is risky. See some earlier posts for more on this.) So, what does that mean for both public health and personal choices? Public Health Choices From a public health standpoint, the goal is and should be to vaccinate as many people as possible with any vaccine that we have as fast as possible. Every day we do 2 million or 3 million shots of anything is a good day. If everyone had the J&J vaccine magically, we would be in a totally different world. Given that demand still outstrips supply, the public health value of having more vaccines available can hardly be overstated. The J&J is also incredibly useful for public health because of the one-shot-easy-storage nature. Many states are talking about using it to vaccinate people who come to the ER, or take mobile vaccine clinics to homeless encampments or other difficult to reach populations. These groups are harder to serve with vaccines which require two doses. From a public health standpoint, this approach is smart, but I will admit to some concern that this will exacerbate the “this is the less good vaccine” view. In fact, the use in these populations has nothing to do with vaccine quality and everything to do with the ease of use. If I were in charge (which I am decidedly not) I would consider also using the J&J on other “transient” populations with less of a stigma. My choice might be on campus college students: mass one-shot vaccination before they leave for the summer. Bottom line: states should use every last vaccine they get ASAP. Personal Choices A lot of people are thinking about this more as a personal choice, though. With the frame of something like: Should I get the J&J if offered, or should I wait for one of the others? It might be easier to tell you how I’m thinking about it. My number one point is that I would get any vaccine offered. I’m teaching in person and we’ve had outbreaks and even though I understand my personal risks are small, I’d feel better if I were vaccinated. If someone told me I could get the J&J today, I would stop writing and cooking stuffed shells right now and go get it. Honestly, I’d probably get the Russian Sputnick V vaccine if it was offered. Novavax? Sure. I’m not giving a way my shot, is my point. And importantly, I would consider myself vaccinated regardless of which vaccine I got. Which doesn’t mean hot basement singing parties or taking off my mask in the grocery store, but does mean I’d go to indoor restaurants and feel more comfortable seeing family and friends in my house, without masks. I wouldn’t make these changes differently if I had the J&J rather than the Pfizer/Moderna. Second point: If a menu of options was in front of me and I got to choose, I’d pick Pfizer or Moderna since I think their efficacy is slightly higher. Underlying my feelings here is the realization that this is not my last COVID-19 vaccine; it’s not any of ours. We are going to be having boosters for a while, as the virus evolves and vaccines evolve to address variants. If you get the J&J now, you’ll probably end up with another shot in a year, maybe from them, maybe from Moderna or Pfizer, maybe from some other source. This may be an annoying revelation, but I think it also dials down a lot of the importance here. You aren’t committing to some vaccine for life.

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