Covid 19 vaccine development

There are over 50 vaccines under research for the covid 19. Robert Baric did some interesting work including gain of function studies creating sars chimera attempting to build vaccines against a sars virus model. His work shows the difficulty posed in creating a safe and effective vaccine.

https://www.nature.com/articles/nm.3985

https://jvi.asm.org/content/85/23/12201

The NY Times has a Coronavirus Vaccine Tracker and it is updated regularly.

According to the article, “Researchers around the world are developing [more than 165 vaccines against the coronavirus, and 27 vaccines are in human trials.” That’s a lot of research!

Thanks. No doubt there is a lot of great vaccine research out there.
The problem is that our public leaders are building an unrealistic case for the vaccine in the public mind.

These studies by Baric specifically point to the difficulties of building a safe effective vaccine especially in the time frame that politicians are suggesting. This virus is very well designed with lots of problems including the furin cleavage Site and the cd 147 T cell target. Baric research points out in His SARS gain of function studies the following challenges.

  1. The vaccine generated immune response quickly fades in animal models.
  2. The vaccine generated immune response accentuated the pathology in viral challenged animal models particulary in the aged animals
  3. The vaccine presented immune response problems when challenged with heterologous viruses.
  4. The vaccine may not be protective against infection but just against developing severe illness.
  5. The long term effects of the vaccine - virus risks need to be assessed. We really need to do extensive animal testing to evaluate these potential risks.

More likely, our leaders (the real leaders who actually pay attention to science and reality) are finding they have to combat vaccine scare-mongerers who are spinning all sorts of narratives to further frighten a public already hopped up on fear. That may involve showing reassurances that, as fast as this vaccine is being developed, it is being done so with all the same (even if accelerated and overlapping) rigorous testing. Nobody (except the fear-mongerers) are making claims that any vaccine is supposed to be 100% effective or remain effective for years. Real science gives us improvements, not panaceas. How soon and how effective it will be are not completely nailed down. But how safe? That will be nailed down with a very high degree of certainty. Still not entirely risk free, of course - nothing is. But by far yours (and society’s) biggest risks taken will be if they refuse a vaccine out of fear. If taking a vaccine scares you, then not taking it should really scare you to death (maybe literally). Just remember next time you get in your car and fasten your seatbelt … there have [apparently] been documented cases where somebody died because they had their seatbelt fastened and could not exit a car when they needed to. So knowing that, do I then refuse to belt up? Absolutely not! Because I know there have been far, far many more deaths from not using restraints than from using them. Those refusing such things out of fear are being irrational - i.e. playing the odds stupidly.

It is worth remembering that the actual infection will produce some of the same antibodies that the vaccine will produce. The advantage of a vaccine is that we can choose which antigens are both protective and the least likely to cause side effects, whereas with the actual viral infection you get all the antibodies, including the potentially bad ones.

The loss of protective antibody titers is also seen with other vaccines, such as many flu vaccines. It may mean getting a shot every 6 months until the spread of the virus is under control, which doesn’t sound all that bad.

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We also put out an article about vaccine development that includes a discussion on COVID development: From Need to Distribution: Vaccine Development in Urgent Times

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Thanks for pointing this out, Scott. Being a realist gets lonely sometimes. While getting a vaccine would be great, very few in the public eye admit that it’s “if”, not “when”. Kudos to Fauci for pointing that out last week and also acknowledging it will never be contained.

What’s more disturbing is that waiting on a vaccine seems to be the only long-term strategy under consideration for re-opening the economy.

And very fruitful research. You need to realize that vaccines aren’t one-size-fits-all. For example, the shingles vaccine I had received was replaced by a new improved vaccine ( SHINGRIX) that you actually need to get 2X. Since I don’t want to get shingles I was grateful to get it and not grouse about getting more injections. I didn’t get side-effects but some people do. That’s a risk I was willing to take. I don’t want to get shingles! I really don’t.

Even when a vax protects for a long, long time, juveniles (both people and animals) often need to get booster shots after an initial round of vaccines. My dogs get some vaccines (e.g. rabies, bordatella) yearly and they don’t complain (and not because they became autistic from the shots).

Hopefully, I’ll soon be taking part in a combined phase II/phase III clinical trial for the pfizer covid-19 vaccine. They’ll be following what happens for 26 months.

I encourage everyone to follow this Coronavirus Vaccine Tracker, which is updated often.

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I hope that we will have a safe effective vaccine expeditiously but the vaccine or bust strategy could be very dangerous if you cannot timely deliver a safe effective vaccine. I think that it would be better to be realistic and underpromise on the vaccine and detail the challenges. Granted there are many new therapies now available that will continue to reduce the death rate and prevent the long haulers but we have a populace that are being told that the vaccine is the only hope. I agree that you can direct the immune response to the antigens you want but you need to do long term testing with viral challenges including other corona viruses to see the potential risks for that strategy. Baric reports that they saw attenuated pathology especially in the vaccinated older animals with viral challenge. This Covid 19 virus Is more pathogenic than the one Baric was using in his gain of function studies and is also targeting T cells via the cd 147 receptor with unknown implications.

To quote Baric a leading expert in SARS research
Our results demonstrate vaccine induced enhancement of eosinophilia and inflammatory response following challenge as well as failure to protect against heterologus challenge in an aged animal model. This work highlights the challenge of vaccine design for zoonotic viruses the need for developing broadly neutralizing therapeutics and the particular difficulty immunizing aged populations

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Those working on vaccines are well aware of the dangers of vaccine-induced disease enhancement. Note that while some SARS candidates caused enhancement, not all did, at least in animal models. There is a good (if slightly dated) rundown of the issues here.

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Sadly, a news story last night said that 40% of people will not take a vaccine. While those of us who will may benefit from greater availability, it means this disease will be circulating a long , long time and herd immunity may be a pipe dream. Of course, if like flu, that may be the case anyway. In any case, a shot or two a year is a small price to pay for return to normal life as @T_aquaticus pointed out.

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I would take those surveys with a grain of salt. A lot of people are uncertain about a vaccine now, but is widely distributed without a lot of problems, views are likely to change.

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Thanks Steve. This virus is especially tricky especially with the cd 147 target. Viruses are great examples of the red queen hypothesis. I am hopeful but cautious and we will see from the data as it develops. One way or the other if the vaccine(s) is proven safe and effective then those in the highest risk groups should receive priority in vaccination.

What is the alternative? Just let everyone get sick?

Your body is going to make those same antibodies in response to a real viral infection.

Then you will also see attenuated pathology in people who have recovered from an actual viral infection.

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Well my favorite quote about this virus comes from Dr. Osterholm. “It’s ok to say we just don’t know.” We both know science is messy and we need to do our due diligence and be sure that the vaccine is safe and effective. The irony here is that the vaccine needs to be at least 50% effective how does that work when at least 50% of nfections are asymptiomatic? Difficult to determine efficacy? I don’t know what the options are if no vaccine but think that we shouldn’t count our eggs until they are hatched a bad vaccine (unsafe not effective) is worse than no vaccine. There are more treatments coming along and just like hiv we will come up with a treatment regimen with or without a vaccine.

I believe that some of these vaccines cause hypersensitivity that results in an attenuated viral pathology that is more then the native viral response.

by testing the clinical trial subjects.

There are treatments available today, e.g. Remdesivir

The expression goes, “Don’t count your chickens before they’re hatched.”

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So to be clear please. What is the endpoint? Is it preventing 50% of infections after exposure? Is it preventing 50% of those exposed to developing disease? Is it preventing severe outcomes?

Any one of those would be valuable, right?

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What is the desired endpoint? I am just curious. These are not the same and since such a high percentage of people are asymptiomatic for unknown reasons it becomes difficult to distinguish effectiveness in certain cases. Then you may see less infections in vaccinated but same or even more deaths than placebo what would you make of that?

For the Oxford vaccine

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