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

post by ChristianKl · 2020-04-09T19:40:15.922Z · LW · GW · No comments

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    CellBioGuy
    JustinShovelain
    avturchin
    Chumpai1986
    micpie
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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?

Answers

answer by CellBioGuy · 2020-04-10T03:56:46.947Z · LW(p) · GW(p)

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.

comment by Chumpai1986 · 2020-04-13T07:24:55.536Z · LW(p) · GW(p)

So you can generate a killed virus vaccine with heat or chemicals as well.

This method just doesn't generate a very strong immune response compared to live attenuated vaccines. You need an adjuvant. I am guessing having some cells infected by a live virus contributes to a full immune response (induce CD8 T cells etc).

answer by JustinShovelain · 2020-04-09T19:59:26.478Z · LW(p) · GW(p)

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.

comment by ChristianKl · 2020-04-10T15:14:51.971Z · LW(p) · GW(p)

You don't need to grow it at scale and out of the two vaccine we have in trials one is adenovirus-based while the other is mRNA-based.

answer by avturchin · 2020-04-10T13:00:29.444Z · LW(p) · GW(p)

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

comment by TAG · 2020-04-10T13:02:34.246Z · LW(p) · GW(p)

Every health organisation requires tests,because untested vaccines are dangerous

comment by ChristianKl · 2020-04-10T16:00:46.325Z · LW(p) · GW(p)

The FDA has emergency use provisions that can be used. There's currently a US president who wants a vaccine as soon as possible and doesn't really care about FDA regulations.

There are probably also plenty of third-world countries that would be willing to use non-FDA approved vaccines..

answer by Chumpai1986 · 2020-04-16T02:22:45.697Z · LW(p) · GW(p)

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.

comment by Chumpai1986 · 2020-04-16T02:26:29.380Z · LW(p) · GW(p)

P.S. in the literature, it does seem (at first glance) that killed vaccines require more doses compared to live vaccines.

answer by micpie · 2020-04-10T05:03:31.327Z · LW(p) · GW(p)

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.

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