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Comment by xoxoy | Hacker News Reader

curious who wins the vaccine race. my understanding is the RNA vaccines being researched by Moderna and Inovio don’t stimulate T-cell development, in which case they seem like poor candidates compared to the adenovirus candidates like the Oxford one that do.

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The Pfizer/Biontech mRNA vaccine did quite well on stimulating T-cell responses. https://www.fiercebiotech.com/biotech/pfizer-reports-strong-...

Good T-cell response has historically come from replication competent virus (live virus vaccine) because the process of replicating their genetic material and producing proteins triggers many of the T-cell responses. Inactivated virus vaccines or protein sub-unit vaccines require adjuvants to trigger these mechanisms and have never given protection as good as live virus.

mRNA and viral vector (which are the leading approaches right now) are very new and try to produce the effect of live virus vaccine without having to first find an attenuated, stable vaccine strain. They do this by using either another virus or a lipid shell to inject genetic material into cells which starts the cells producing proteins.

I would expect both the Moderna and the Oxford vaccine to give some T-cell immunity as well as antibodies.

Moderna (mRNA), Pfizer (mRNA) and Oxford (viral vector) have all reported T-cell activity. Sources:

* https://blogs.sciencemag.org/pipeline/archives/2020/07/15/mo...

* https://blogs.sciencemag.org/pipeline/archives/2020/07/20/mo...

* https://blogs.sciencemag.org/pipeline/archives/2020/07/20/ne...

(these blogs link the actual preprint primary source as well)

so mRNA vaccination is an offshoot towards technology which was created about a decade and a half ago to make more efficient monoclonal antibodies for the lab. The process is to extract B-cells from a challenged organism (almost always mouse) and then fuse them as 'hybridomas' with immortal cancer cells, select single cell clumps that show an immune response out of multi-well plates, and then use those immortalized cells to make that one antibody forever.

So indeed the mRNA vaccines come from technology that is highly optimized to elicit a B-cell response. (Not to say that it doesn't stimulate T-cells, but I wouldn't be surprised if it didn't).

Wait I’m a little confused. It seems like injecting people with an mRNA, which their cells then translate into an antigen that provokes an immune response, is a very different technology from monoclonal antibodies. They are both related to the immune system, but mRNA vaccines are at least partially about stimulating polyclonal antibody production, as opposed to monoclonal antibodies. Can you articulate why you think mRNA vaccines were derived from monoclonal antibody work?

I just remember talks (I was at a cutting-edge immunology research center, The Scripps Research Institute in San Diego) about using mRNA vaccination in the 2007-2009 era to make monoclonal antibodies. Oddly, I can't find any publications from that era on it (but I can find a few papers from 2017-2019 using that exact methodology), so it appears that either i was mistaken, or it quietly pivoted to human vaccination as a target. It's really not possible for me to be mistaken about the timeframe, though, since I have been out of biology since 2015.

The mRNA vaccine field isn't related to monoclonal antibody production.

This is very confused. The hybridoma process you describe is the only way to make monoclonal antibodies, not a more efficient way, and it was invented in the early 1970s. It has nothing to do with mRNA vaccines.

Both mRNA vaccines so far have produced T-cell responses with Pfizer/BioNTech producing more CD8 than Moderna. Both had detectable levels of responses, though. As is typical in clinical development, we need to wait for the phase 3 data before making a decision.

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