Moderna’s Phase I/II Results
Moderna has finally published intreim results from their Phase I study — 8 weeks after teasing them in a press release — and the picture is generally positive. Their mRNA vaccine raised a dose-dependent immune response in all 45 subjects tested.
Dr. Anthony Fauci told The Associated Press, “No matter how you slice this, this is good news.”
Here is the paper in the New England Journal of Medicine. It’s fairly readable as such things go. I definitely do not know enough about immunology to understand the finer points in Moderna’s data; for that I lean as usual on Derek Lowe. He links to the Twitter feed of an RNAi therapeutics analyst who points out a weakness in the immune reaction (poor CD-8 T cell response) Moderna describes in their paper.
Moderna also details undesirable side effects reported by their study subjects. It is a bit daunting to envision a vaccine that causes so many uncomfortable (but not actually dangerous) reactions being given to millions of people.
Moderna’s stock (ticker MRNA) popped yesterday on the news, dragging the Dow Jones Industrials up along with it.
You’ll recall that a couple of weeks back Moderna announced a schedule slip on their way to Phase III testing. They are now back on track to begin a trial with 30,000 subjects on July 27. This puts them neck-in-neck with Pfizer’s first candidate vaccine. Lowe points out that, comparing the Phase I/II results of the two candidates, Pfizer’s seemed to exhibit milder side effects; and Pfizer did not publish their T-cell profiling, so a comparison can’t be made on that basis.
What an interesting and consequential journey toward a vaccine – one of these days… Thank you, Keith, for your constant and excellent information on this blog!
For those who aren’t aware: the CD8+ T cells (aka killer T cells) go after your own cells that have already been invaded and co-opted by the virus. Their job is to shut down the unwanted virus factories.
In contrast, the antibodies go after viruses that haven’t yet invaded a cell. The CD4+ T cells (aka helper T cells) direct the B cells in the production of new antibodies. Those new antibodies will supplement and replace the antibodies that are already present; the latter is the primary measurement being used for the vaccine.
Doug, do you happen to know, what is the lifetime of a cell that a (this) virus has taken over? Does it keep producing viruses indefinitely, or perhaps suffer some resource depletion and quit after a while?
The cell certainly will die on its own. I have no idea what the numbers look like for SARS-CoV-2, which seems to infect lots of different cell types, but I found a paper on Influenza A that showed average cell lifetime of approx. 11 hours, average lifetime of the produced viruses of around 3 hours, and an estimated R0 of 22 with wide confidence limits (5.1 to 46.1). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563736/
Back in the dark ages of this virus, the NY Times said, “Each infected cell can release millions of copies of the virus before the cell finally breaks down and dies.” Information from that time period isn’t super-reliable, though. https://www.nytimes.com/interactive/2020/03/11/science/how-coronavirus-hijacks-your-cells.html
[Not responsive to the question, but generally informative] I came across this article from Smithsonian about the immune system and vaccines, relative to SARS-CoV-2. I think it should’ve spent a few words on discussion of the various kinds of antibodies (e.g., IgM and IgG), though. It also doesn’t make clear that the different functions of T cells are performed by different kinds of T cells. Still, it seems a good overview of the basics. https://www.smithsonianmag.com/science-nature/coronavirus-immunity-complicated-180974970/