Well, figured the daily COVID threads haven't been that productive lately, so thought maybe if we try to discuss one really important COVID-related topic that is very much science-driven, perhaps we can keep this on topic, i.e., the science behind the vaccines, the status and progress of the ongoing clinical trials with regard to both safety and efficacy, and in what ways vaccine deployment can hopefully allow us to keep the novel coronavirus at bay, if not beat it into submission. The NY Times vaccine tracker is a great resource, as is the occasional update of the vaccine landscape and key breaking news for the major vaccines by Derek Lowe (In the Pipeline Blog). In addition from a more scientific perspective, the video below by noted virologist, Dr. Krammer, which is a little over a month old, is still one of the best resources out there on the science involved with each of the major vaccine candidates. Let's see how this experiment goes...
NY Times Vaccine Tracker
Derek Lowe's In The Pipeline Blog
Dr. Krammer's Video on Vaccines
In addition, I'm providing an updated (from a post of mine a few weeks ago) bulleted summary of the 9 vaccines that are currently in pivotal phase III clinical trials, which will determine the safety and efficacy of each vaccine candidate. We're really getting down to brass tacks soon, with the pivotal phase III trial results likely only about 6-12 weeks away and I'm still optimistic we'll have an approved vaccine by the end of the year; approvals before Thanksgiving seem very unlikely however, given how much data are being generated and how much there will be to review prior to approval. All of the vaccines had reasonably good safety profiles and implied efficacy (prompting good immune responses) in phase I/II, so far, meaning no major red flags, but these were obviously in smaller phase II trials w/o any data on conferring immunity yet.
Keep in mind that all of the vaccines in phase III right now will require an initial shot and then a booster shot (typically a month later) to achieve optimal immunity, with the exception of the J&J (Janssen) vaccine which is looking at a single shot. Some of the vaccines that are a few months behind the frontrunners, like Novavax (in phase II using proteins doped onto adjuvant nanoparticles, which is about to be approved for influenza) and the Merck/Themis vaccine (in phase I using the measles virus vector platform, which is proven) are looking at single shots and possibly greater immunity levels; there are dozens more than those two and the Times article does mention about 42 phase I/II vaccines in development. Also, remember that the FDA is saying a vaccine is "effective" if it can "prevent disease or decrease its severity in at least 50% of people who are vaccinated," so it's possible efficacy will look similar to the flu vaccine (although most experts expect much greater than 50% protection).
- Moderna's mRNA vaccine; no mRNA vaccine has ever been approved before; requires -20C cold chain (freezers)
- Pfizer/BioNTech's mRNA vaccine - requires -70C cold chain for stability of the formulation (dry ice storage typically - probably not a huge issue in first world countries, but a major issue elsewhere)
- Astra Zeneca/Oxford's chimp adenovirus viral vector vaccine (only 1 vvv has been approved - Merck's Ebola vaccine). A hold was placed on this phase III trial to resolve 2 observations of transverse myelitis (spinal inflammation, not too dissimilar from Guillain-Barre Syndrome, which was a major issue with the Swine Flu vaccine in 1976) - the hold was released in most of the world, but not in the US.
- CanSino's human adenovirus viral vector vaccine; human adenoviruses might have pre-existing immunity issues
- J&J's human adenovirus viral vector vaccine (using an obscure human virus, hoping to avoid the pre-existing immunity issues); this one starts phase III any day now.
- Russia's Gamaleya Institute's human adenovirus viral vector vaccine (already "approved" in Russia - a PR stunt)
- There are three Chinese vaccines (one by Sinovac and two by SinoPharm) using "old school" deactivated actual coronavirus (most vaccines in use today use this approach, but it's much harder to scale and often less potent, but it works usually); two of these also have "emergency use approvals" without phase III data, which is also dumb.
- The last one is an oddball. It's a trial of the existing Bacillus Calmette-Guerin vaccine for tuberculosis in Australia.
Note that the three front-runners in the US, Moderna, Pfizer/BioNTech, and Astra Zeneca/Oxford, all very recently published their phase III clinical trial protocols, which was a huge step forward with regard to transparency as these protocols lay out exactly how the trials are being run with how many people in each sub-population, as well as what the expected criteria for success are (how many infected in the treatment/placebo arms, as well as the severity of the infections and all the math behind calculating "vaccine effectiveness"). It's pretty complicated stuff that Derek Lowe covered really well today in his latest blog, so I refer you to that.
https://blogs.sciencemag.org/pipeline/archives/2020/09/21/the-vaccine-protocols
In addition, here are a few more interesting links on some key issues for these vaccines. The first one is another Lowe blog entry, this time on what exactly "cold chain" means for vaccine stability, supply chains, and availability, especially in the 3rd world. The 2nd one is also a Lowe blog, on what can sound like a mundane topic, but it really isn't, as it's on things like ensuring there are enough glass vials or silica-coated vials for billions of doses and ensuring that the vials used are gas tight (a key for stability), which is no trivial task. I've done a lot of work in both of these areas over the years for new pharmaceuticals and they're not as "sexy" as the actual product, but if mishandled, they can derail an entire product launch.
https://blogs.sciencemag.org/pipeline/archives/2020/08/31/cold-chain-and-colder-chain-distribution
https://blogs.sciencemag.org/pipeline/archives/2020/07/08/materials-and-gases-vials-and-vaccines
