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Suppose a person with COVID-19 coughs into a bag. Let the bag sit in the sun for, say, 72 hours -- so as to make the virus inactive.

Could a healthy person breathe in the inactivated virus from the bag (perhaps done multiple times) to (eventually) trigger an antibody response to the virus?

Is this a known way to make inactivated vaccines? Has it been studied, perhaps for other viruses?

Are there known reasons why this would not work?

Peter Mortensen
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unutbu
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    Coughing in a bag and leaving it in the sun may be cheap and easy: those aren't the hard parts. The hard parts are having a vaccine that produces enough of an immune response to protect against future exposure, and a vaccine that is safe enough to not cause illness directly in the people it is given to. Once you plan to test those two things, well, it turns out there are much more reproducible ways to do the cheap and easy steps. – Bryan Krause Apr 20 '20 at 22:38
  • Suppose this cheap and easy method was subjected to the same 4 phase testing as a normal vaccine. If it passed, it would have an advantage over normal vaccines of being more cheaply and quickly implementable all over the world. Unless there is an a priori reason why this wouldn't work, wouldn't that advantage mean this method warrants consideration? – unutbu Apr 21 '20 at 00:23
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    'Unless there is an a priori reason why this wouldn't work' Quality control. As @BryanKrause point out, you need something that's safe but effective. With your method you have no control over how many virons are coughed into th bag, and you don't know how many are killed in the sunlight. Each time you tried this it would be pot luck whether you were just infecting them with the disease, or just wasting their time because no immune response was provoked. The hard work of producing vaccines is creating something that works reliably for many different people. – Charles E. Grant Apr 21 '20 at 01:33
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    You might look on this at some of the questions on variolation on this site. This was a crude form of vaccination for smallpox. You'd collect some scabs from smallpox blisters and rub them into a cut on an uninfected person. If they were lucky they got a mild case of smallpox and were then immune. If they were unlucky they got a bad case of smallpox and died. As with your suggestion, there was no way to calibrate the dosage. – Charles E. Grant Apr 21 '20 at 01:42
  • @CharlesE.Grant: unfortunately, we don't have a good answer on that yet (on this site): https://medicalsciences.stackexchange.com/questions/23204/are-there-any-epidemiological-or-laboratory-studies-on-the-effectiveness-of-vari – the gods from engineering Apr 21 '20 at 06:19
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    Are there known reasons why this would not work? I think the more important question is - is there any evidence whatsoever that suggests this even remotely has a hope of doing anything beneficial at all. I'm curious about what would give you the idea that this could possibly be effective? – J... Apr 21 '20 at 18:01
  • If the virus is inactive, it wouldn't do much good as a vaccine, would it? – Mast Apr 22 '20 at 07:20
  • @J...: "Inactivated vaccines use the killed version of the germ that causes a disease". The SARS-CoV-2 virus has a lipid membrane. I am speculating that time and sun break down the membrane (or some other part), so as to make the virus ineffective at penetrating cells. Nevertheless, enough fragments of the membrane may exist so that exposure to them may stimulate the immune system into producing antibodies. That is the layman's understanding I used as the basis of my question. – unutbu Apr 22 '20 at 19:50
  • @unutbu Plenty of things are simple in principle. I guess I was wondering if there was any particular evidence that the method you've proposed has ever been tested and used effectively. Vaccine development is expensive for a reason, after all... – J... Apr 22 '20 at 20:16
  • @J...: This might have been a stupid question, but I didn't know the answer, so I asked it. While the expensiveness of drug development hints strongly that there is no simple solution, drug companies would also have no motivation to pay to study this since there is no opportunity for profit. So I'm looking for basic science research which might explain why this wouldn't work. – unutbu Apr 22 '20 at 20:30

2 Answers2

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The only approved inhaled vaccine is the flu vaccine delivered intra-nasally. It uses a live attenuated virus. There are a whole list of people who should not receive it because it's a live virus, and it works better for children, but only is 40% effective for adults.

The main issue is

The intranasal LAIV, recommended for children above the age of 2 years, induces a broader immune response wherein protection is not antibody mediated and probably involves undefined multiple correlates of protection.

and that's with a live virus.

How well would a dead inhaled virus work? Well, we have some data from MERS that suggests that vaccination with whole dead virus can increase lung pathology when exposed to live virus.

The implication of the current study is that application of an inactivated MERS-CoV vaccine for prevention of MERS in humans may carry a risk for lung immunopathology if subsequently exposed to MERS-CoV. The study also leads us to suggest that the extensive background of preclinical experience with inactivated SARS-CoV vaccines may be applicable to inactivated MERS-CoV vaccines.

So, your cheap vaccine may increase your risk of death or disease when exposed to the live virus.

Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines https://www.cdc.gov/flu/prevent/nasalspray.htm

Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027702/

Graham Chiu
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It wouldn't be consistent. (as some of the commenters pointed out).

Here are some numbers:

  • The concentration of virus in sputum can vary by a factor of 10^5. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224694/ for count of RNA in sputum)

  • Best guess is that 100-1000 RNA copies is a "quanta" in the Wills-Riley Model (http://tinyurl.com/covid-estimator)

  • If it's known how many RNA copies is good to generate immune response but not disease, it's very hard to get the right level.

  • There will be variation in immune response / disease contracting.

But, this doesn't rule it out as possible. In fact, nothing can prove it's impossible except running every variation of what you're saying. To prove it's possible, you would need to run the controlled experiment.

But that experiment would be considered unethical.

You could try it in rats or mice first. But there is no good animal model for COVID19 right now (from what I read).

chongman
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