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Why don't we have active human trials with inactivated SARS-COV-2?

by ChristianKl1 min read9th Apr 202010 comments

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Coronavirus
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It seems to me that it should be relatively straightforward to grow SARS-COV-2 in vitro and then inactive it via UV radiation.

After we inactivated it we could give it to test subjects to see whether we get a good immune response.

Is there a reason this is more complicated then I think? Have I missed something else? Otherwise what's the reason that there are no such trials going on?

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I'm not an immunologist, I don't even play one on TV.

There are a large number of potential vaccines for the SARS-2 virus being studied, including one inactivated virus vaccine from what I have seen, but there is already a decade of work in the can on vaccines for the related SARS and MERS viruses. This work was slow compared to whats happening now due to lack of interest, eradication, or poor human to human transmission, but now can be built on very quickly. This work tells you where you should focus your effort.

It was found that several of the ways of inactivating the first SARS virus to create a vaccine caused WORSENED disease upon immunized animals later actually getting exposed to the real virus, due to a number of mechanisms including (to oversimplify) inducing the wrong kinds of antibodies that helped trigger inflammation as well as enabling non-neutralized viruses to get inside or hyperstimulate immune cells. Most work now is focusing on the types of vaccines that wound up not having that sort of problem for these related viruses, only showing the body the recombinant spike proteins or fragments of the spike protein and maybe some of the intracellular proteins. They get to be displayed either on body cells by a DNA/RNA vector or as recombinant irritating protein infusion or get displayed on a *different* modded dead virus that does not generate these problems.

The dead virus does not generate the same immune reaction as a live one since infected cells contribute signaling molecules and context, and some (but not all) dead viruses can generate immune reactions that should not happen normally.

I think virus inactivation is a normal vaccination approach and is probably being pursued here? The hardest part is probably growing it in vitro at scale and perhaps ensuring that all of them are inactive.

Even if God appears in the sky and brings us a vaccine, the FDA will require at least 1 year to test its safety.

I just wanted to add another response here, after thinking about it for a few days. I've read a papers where killed HIV vaccines etc seem promising. So, I think this is a viable strategy, but there are a few issues. As I wrote in my other comment, you are probably mainly stimulating an antibody response, but not a cellular response.

The issue with using UV, it probably a higher chance of viral re-activation. You would probably use gamma irradiation, maybe with heat and chemical treatment also. The issue with inaction is that you potentially alter the antigens.

The other issue is that RNA viruses mutate quite fast. So, you may get vaccine escape variants. This is more so an issue if vaccine distribution takes many months to roll out. Whilst at the same time the virus is circulating in the population. You may end up vaccinating everyone against one strain but not others. I am unsure but perhaps some mutation that occurs during a live attenuated vaccine may help ward against this.

To grow the virus and inactivate them by chemical reagents is the standard setup for (older) influenza vaccine systems that are egg- or cell-culture-based. From such a setup whole-virus- or subunit vaccines can be derived.