From 2008 until 2013, I went back to Cornell part-time to finish up a BA in Molecular Biology. It’s an interesting field that didn’t even exist during my first shot of college. Mol Bio kinda squoze into the gap between Biochemistry and Genetics, with big help from the Human Genome Project.
Molecular biology is the reason you can get vaccinated for Covid-19 now. Previously, it took a minimum of 4 years to develop and test a vaccine. What sped things up is mastery over the big molecules of life: DNA, RNA and proteins.
Derek Lowe is a molecular biologist who blogs for Science magazine. He’s an expert on diseases and vaccines, but he writes for mere mortals. If you want to make intelligent decisions about Covid-19 vaccines, here are links to some of his recent posts. They are way better than anything you’ll ever see on Twitter or Facebook.
B Cells, Infection & Vaccination
J&J and Novamax Vaccines
Vaccine Production Myths
Why Lower Efficacy Isn’t That Bad (Vox)
I’ll try to summarize vaccine results so far, in very over-simplified form.
The first Covid-19 vaccines approved in the US were RNA vaccines from Pfizer and Moderna. Both require two jabs, with about 94% efficacy at preventing infection. They use mRNA that includes the code for Spike protein. It’s stuffed into a tiny sphere of fats, cholesterol and probably some proteins. Composition and size similar to a Coronavirus, or like LDL “bad cholesterol” plus RNA. When injected, the nanoparticles are absorbed by muscle, lymph and liver cells. Inside them, the mRNA hooks up with a ribosome, which uses its sequence to build Spike proteins. Some Spikes leave the cell, float around, and trigger the immune system. Later, a real Coronavirus comes along, but immune cells recognize its spiky bits and send in the killers. Protected!
The Oxford/AstraZeneca, Johnson & Johnson/Janssen and Sputnik vaccines use a different approach. Instead of nanoparticles, they deliver via a modified Adenovirus (a mild virus that causes sore throats, pink eye etc). The DNA code for Spike is spliced into its genome. After injection, the virus infects some human cells. Its DNA sneaks into their nucleus and is transcribed into mRNA. That exits the nucleus, then follows the same path as the RNA vaccines: ribosome to Spike to export to immune response.
Of the 3 DNA vaccines, Sputnik (2 jabs) has excellent results, but probably won’t be available in the US. J&J (1 jab) is mediocre at preventing infection, though it’s OK at blocking serious disease and death. Oxford (2 jabs) is somewhere in between. The lower efficacy may be because some people are already immune to Adenovirus: so they kill it prematurely. Sputnik uses two different virus forms, which may explain its better performance. J&J and AstraZeneca are testing variations that may also be more effective.
Novamax takes a third approach. It cuts to the chase, and injects Covid-19 Spike protein directly. The Spikes are manufactured by moth (!) cells. How cool is that? To produce the vaccine, the DNA sequence for Spike is spliced into a virus genome. That infects the moth cells, which then produce Spike via the same path as the DNA vaccines. The protein is purified, then attached to a fatty nanoparticle. To the immune system, it looks a lot like a Coronavirus. Trials in the UK showed 89% efficacy (2 jabs). US Phase 3 trials started in December.
The DNA and protein vaccines have a big advantage: both molecules are more stable than RNA. They only need fridge temperatures for distribution instead of freezers (Moderna) or dry ice (Pfizer).
As an old dude, I’m eligible to be vaccinated now. The original plan was to wait for J&J vaccine data before deciding. That quickly became moot, since there’s a huge backlog. It will be a while until I can get any vaccine regardless. By health and habits I’m low-risk, so it won’t be too bad to live the pandemic lifestyle for a few more months.
New York vaccinated nursing homes and health care staff first. Now the priority is essential workers and teachers. That approach is already having an impact. There were 20+ daily cases in the local hospital for the month after Christmas, but it’s down to 3 or fewer. Surrounding counties are also doing much better.
At the moment I probably would pick Novamax, if its US trials are similar to the UK results. I probably already have Adenovirus immunity, and it makes sense to save mRNA vaccines for the next pandemic. However, the decision is barely more than a guess. There may not even be a choice of vaccines.
The big picture for humans: the success of all these vaccines is extremely good news. They’re fast, and will be even faster to release in the future. Minor DNA/RNA/protein tweaks to keep up with mutations will only take days, and won’t need such a long approval process. All three of the methods will help fight other diseases. And that’s not even counting newer techniques like CRISPR that are gradually being developed.
Looking back ten years from now, Covid-19 may seem like a wonderful disaster that launched huge medical advances.