Vaccine futures

Have we reached the point where we can speculate about vaccine timelines?

“When will we have a vaccine?” is a question that I get asked on the regular. I think when the pandemic started, this was anybody’s guess, but with several vaccines entering Phase 3 trials, we are nearing the point where we can begin to speculate about the answer.

The first thing we need to understand is the different types of vaccines. The Moderna and Pfizer-BioNTech vaccines are both nucleic acid vaccines; they include an mRNA that codes for critical parts of the virus, hoping to enlist the patient’s own cells to produce these components and create an immune response. This is a relatively untested vaccine design, and so their early results showing strong immune responses are very impressive for the technological concept as a whole — even if we can’t be sure that the immune response seen is protective.

Another vaccine concept is the ChAdOx vaccine. This is being developed jointly by Oxford University and the pharmaceutical company AstraZeneca. It uses a chimpanzee adenovirus — similar to a human upper respiratory virus that causes colds — that has been genetically altered so that it cannot replicate in humans. This virus has also been altered to produce the “spike glycoprotein” (S) of the virus that causes COVID-19. For what it’s worth, the mRNA-based vaccines also target the S protein.

Here’s a video describing human trials for the ChAdOx1 nCoV-19 vaccine:

The ChAdOx vaccine seems most promising to me because it uses a respiratory virus as its vehicle, and thus gives the immune system more of a “rehearsal” for a real infection with SARS-CoV-2, the virus that causes COVID-19. Generally speaking, the closer a vaccine can be to a natural infection without causing disease, the better. This helps to stimulate the most relevant parts of the immune system that will respond to a natural infection, and hopefully creates the most relevant protection.

But, like I said, the Moderna data were impressive. It could be that their design is enough to get the job done. The following figure, from the publication in The New England Journal of Medicine, is very compelling. What we are seeing here is the amount of virus that it took to infect cells that had been treated with blood serum from vaccinated patients, following vaccination. In serum collected by day 36, for all doses of the vaccine, it took about 100 times as much virus to infect cells as it did on Day 1 (I’m approximating for brevity here). For reference, some of the best antivirals we have only reduce the replication of the virus they target by a factor of 10 or so. This is very encouraging, but it’s not a guarantee the vaccine is actually protective.

Time will tell which vaccine candidate is going to work out, and there are quite a few in development besides these few. What we’re interested in here is vaccine futures. To do that, let’s first take a look at where vaccines are right now.

The New York Times has a coronavirus vaccine tracker, found here:

This tracker shows one vaccine approved (it’s an emergency approval for Chinese soldiers, nothing to get too excited about) and 4 that are headed for Phase 3, large scale trials. ChAdOx is one of these.

Let’s imagine that of the most advanced vaccines, these Phase 3 trials continue to progress well. They will take time. As a benchmark, Moderna is planning to get its vaccine into the first Phase 3 patients by the end of July, with the first results expected by November. 4 months for a Phase 3 trial — this is very ambitious, but not unreasonable. So let’s use that estimate for our future timeline.

4 months from now, we might have the first results telling us if there is a vaccine that is safe and effective. That would be approximately 12 months from when the virus first infected a human (as far as we know), a truly unprecedented timeline. For reference, the Hepatitis B virus was discovered in the 1960s and the first vaccine against this virus was approved in 1981. So, 12 months is an incredibly fast development timeline.

Now we need to think about the timeline to approval. From the moment that data become available, I can pretty much guarantee that the review and approval of a COVID-19 vaccine will be the most important priority at every regulatory agency around the world. I would not expect the review to take more than a month or two, for better or worse. So that ups the timeline to 6 months, at the outside.

Companies are already manufacturing these vaccines “at-risk,” meaning that they are making doses even though they are not sure that their product will be approved. I do not expect this to mean that there will be enough doses to vaccinate everyone right from the start. Instead, I would expect that the initial number of doses that will be produced will number in the tens of millions, but I also expect manufacturing capacity to increase exponentially from approval forward. If 10–50 million doses are made over the next 6 months, then I expect 100–500 million to be made over the 6 months after that.

I’m not a supply chain expert, so I can’t be sure of these estimates and I also can’t speak to the timeline of delivery to market. What I can do is say that I think it’s reasonable to expect the first doses of this vaccine to hit US markets by Q1 2021, and they will likely go first to healthcare workers and high-risk individuals. By Q2 2021, I expect the vaccine to be more widely available for most adults who will seek to get vaccinated — this expectation is based on the fact that about 160 million doses of influenza vaccine are manufactured for each flu season. By Q3, I would expect there to be enough supply for us to have a substantial stockpile of the vaccine and perhaps even additional approved candidates to add to the supply.

So, summarizing the milestones, here’s the future I see:

  • Approval of a vaccine candidate by December 2020 at the earliest
  • Availability of doses for high-risk people and healthcare workers by January 2021
  • Availability for most adults beginning in February or March 2021, but with shortages resulting in gradually increasing availability through May 2021
  • Supply that fully meets demand and allows wide vaccine coverage by June 2021

What does this mean for our lives? I would expect that schools will be able to reopen without having to close again by January 2021, as I would also expect teachers to be among those prioritized for early doses. But the virus will remain with us, and we will probably need to continue social distancing and masking efforts until the June 2021 time point.

This article originally appeared in my daily newsletter, COVID Transmissions.

Virologist, author, damn fool. Also found at and Opinions my own, impressions yours.

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