Vaccine Strategies and Bears
How can we stretch out vaccines to hit the widest population, when should we administer a second dose, and why are Looney Tunes so good?
I will eventually shift back to talking about COVID outbreaks and numbers, but most of the news is surrounding vaccine news and distribution, so I guess that is what this newsletter will be about for a while.
Vaccine Stretch Goals
A Second Dose Is a Secondary Concern
Looney Tunes: Wabbit Trouble
Vaccine Stretch Goals
The good news is there is good news: There are a number of plausible strategies for taking our limited supply of vaccines and stretching them out to inoculate more people.
As vaccine roll-outs continue, we keep learning new and often encouraging lessons. One of those is that there is strong evidence that the Moderna vaccine provides identical immune response in younger individuals (under 55) with half the recommended dose. That means (pending FDA approval) we can use it to vaccinate twice as many individuals with half-doses.
The second stretching strategy is to take the available vaccines and use them immediately instead of holding onto them. This has been an idea that has been floated since before we even started giving the first vaccinations, but it’s an idea that has become more and more conventional wisdom as we have moved forward. It’s now coming from some pretty high-level public health professionals, particularly in response to worries that the COVID-19 variant increases transmissibility (I’m committed to diving into that topic in a later newsletter).
This has led some to worry that we won’t have the second dose available when it comes time to administer it 3 weeks after the first shot and I am really kind of excited to share that we should worry less about that because I learned something new about vaccines and vaccine schedules and I love sharing the things I learn.
A Second Dose Is a Secondary Concern
I’m really glad for the people I’ve wandered into in 2020. It’s an absolute joy to learn things and as much as I dislike Twitter for many things, it is still a place where I discover a half-drunken thread from someone who really knows what they are talking about.
A friend introduced me to this thread, which answered a lot of question and so I am going to steal all her information and present it as my own.
To start out: why do we have a 3 week waiting period between the two COVID vaccine shots? To answer this question, we have to back up and bit and talk about vaccines, what they do, and how our bodies respond to them.
The basic role of a vaccine is to fake an illness. We want our bodies to recognize that something is going to attack it and generate antibodies to protect us against the invading pathogen. Vaccines are about creating little cardboard training copies of the virus that wants to kill us and giving our body practice fighting them off. Our body produces antibodies to fight off the virus so that when the real version of the virus shows up, we can defend ourselves.
With many vaccines, our immune systems have a memory. They create antibodies to fight the fake cardboard virus in the first round, but that defense can fade. When the second shot is administered, our bodies look at that and say “oh no you don’t” and, having remembered how to create the appropriate antibodies, they flood our system with them and generate a much stronger immunity.
What is crazy about the COVID vaccine is that a 3 week waiting period is not the recommended waiting period. It’s the recommended minimum waiting period.
What we *don’t* want is for the body to take the second dose and interpret it as the same infection as the first dose. If we do that, then our bodies say “oh, that’s just the disease we were already beating, no need to worry about it”. That’s why we can’t give the second dose a week later.
Instead, we want our bodies to say “What? This thing again?!? Stupid virus, let’s see how you like it when I crank this up to 11!” That’s the antibody flood that gives the longer lasting, more resilient immunity.
The author of the thread above takes note that she is actually surprised that a 3 week waiting period works. It is below the second dose schedule for any existing vaccine, which ranges from 4 weeks to 3 years. With the COVID vaccines, it looks like we could probably safely push back the second dose some distance (possibly 12 weeks? there is very little literature on this) and get more people their first dose while doses are still scarce.
But if we can give the second dose so much later, why are we scheduling second doses at three weeks? I’m glad you asked.
Operation Warp Speed is exactly what the name implies. It is an attempt to put the vaccine approval process on greased rails with a rocket strapped to the caboose. That means they started giving trial participants the second dose as soon as possible. I suspect that they probably gave some participants the second shot at 2 weeks, 4 weeks, 5 weeks, etc. But the goal wasn’t to find how long we can wait to get the booster. The goal was to demonstrate efficacy as fast as possible.
As soon as vaccine producers saw promising results from the earliest test group, they moved forward to seeking FDA approval. It’s extremely likely that immunity persists much longer than 3 weeks. In a normal Phase 3 vaccine study, they would test this over years and figure out exactly the best upper and lower bound parameters for second dose administration. But right now…
And so the emerging consensus is to get twice as many people into the first-stage immunity as fast as possible and then focus on the more resilient second stage as vaccines become more plentiful in the coming months.
Looney Tunes: Wabbit Trouble
This is an early Bugs Bunny / Elmer Fudd short (which we can see as Fudd’s character will develop substantially in later cartoons. Elmer is taking a vacation out to Jellostone National Park for “west and welaxation”. Pitching his tent over Bugs’ rabbit hole starts the cascading series of pranks Bugs plays on him, tricking him into a poor sleep schedule, luring him off cliffs.
The dialogue is hilarious. In the middle of one of the gags, Bugs looks into the camera and says “I do this kinda stuff to him all through the pictcha”. When confronting a hostile bear, Elmer pauses to look up how to respond to a bear and reads the appropriate response out loud.
Parts of this short really highlight the differences between Disney and Warner Brothers at this point in history. In this short, Elmer flees a bear and the background turns into an indistinct blur. Indistinct blurs are easy and cheap to produce. By contrast, if we look the cartoon Pluto’s Judgement Day, the animators took time and imagination to create background drawings that reinforce the theme and tone of the short.
This is really funny! It’s got a lot of gags that Walt Disney would have dismissed because they are too “easy”, like breaking the fourth wall or having Bugs make meta-commentary on the short. But it works. We laugh. It’s subversive and unexpected and it gets a good laugh and honestly what more do you want out of a cartoon than a good laugh?
If we think broadly in terms of two groups, the relatively small high risk group and the much larger low risk group, I think a strategy that ought to be considered is giving two doses to the high risk group and one dose to the low risk group (assuming manufacturing capacity hasn't yet met demand by the time the low risk group is being vaccinated).
The vaccines seem to be pretty efficacious with a single dose. Likely in the range of 90% efficacy. Of course more data would be tremendously valuable here, but based on the data we do have and our knowledge of other vaccines this is a reasonable number.
Vaccinate frontline healthcare workers (however that may be defined, but ideally just those working with covid patients and those distributing vaccines) and those 65+ with two doses.
If we're still not able to manufacture enough vaccines to immunize the general public by the time those high-priority groups are done, switch to a single dose schedule.
Why divide it up like this?
The first group is relatively smaller (16% of the population) and makes up a large majority of hospitalizations (50%) and deaths (75%). The goal is maximum immunity to reduce those outcomes.
The second group is larger and significantly less likely to need treatment. The goal is to reduce spread. Vaccinating two people with 90% efficacy is much better for this goal than vaccinating one person with 95% efficacy.
I also believe that once the high risk group is vaccinated, which again only requires 15-20% of the population to get their vaccines, hospitals will no longer be under any risk of being overburdened and life should return to near normalcy. Continue to carry out single dose vaccinations for the rest of the population, ideally based on age brackets, but lift restrictions asap.