The Power of Vaccines

Most people understand the basic idea of a traditional live-attenuated or killed vaccine–the vaccine gives the body’s immune system a sneak peek at the virus so that when a wild type attacks, the body’s immune system has been trained to fight. It’s less well understood, however, that the newer, designed vaccines, can be better than traditional vaccines and better even than immunity from exposure to the wild virus because a vaccine can now be designed to target the immune system on the weakest part of the virus:

NYTimes: One beauty of vaccines — and one of their great advantages over our body’s natural reaction to infections — is that their antigens can be designed to focus the immune response on a virus’s Achilles heel (whatever that may be).

…The immune response generated against a virus during natural infection is, to some degree, at the mercy of the virus itself. Not so with vaccines.

Since many viruses evade the innate immune system, natural infections sometimes do not result in robust or long-lasting immunity. The human papillomavirus is one of them, which is why it can cause chronic infections. The papillomavirus vaccine triggers a far better antibody response to its viral antigen than does a natural HPV infection: It is almost 100 percent effective in preventing HPV infection and disease.

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There's a thing I didn't know. Is a price in safety paid for the greater effectiveness?

From what I read in How Innovation Works, I’m thankful I wasn’t around for the first polio vaccines. I think Malcolm Gladwell did a podcast on it also — at least something very similar, viruses that cause tumors.

Not trying to bash vaccines. Just giving a concrete example of a vaccine that has become safer. I’m sure there are a lot of other, less controversial, examples I’m not familiar with.

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The greater effectiveness is due to more specificity with the man made monoclonal AB. So theoretically it would safer due to less chance of cross reactivity and then attacking somewhere/thing else in the body.

"theoretically it would safer": if experience in practice backs that up it's excellent news (well, news to me).

Has such a wheeze ever worked for a coronavirus?

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According to extant data that I have seen: No.

Which stands to reason. Traditional vaccine approaches are a bit of a shotgun approach. You either denatured the virus and hoped that none of the immunogenic epitopes were too close to any important self-epitopes (which can be challenging if you have inconsistent protein fragmentation given the many possible combinations of epitopes and genetic variability in the patient population) or you attenuated it so that it retained most of its epitopes but was no longer dangerous (and prayed that it did not have easy reversions or pick up troublesome genetics during serial passage). In both cases, production required high precision to maintain uniform vaccine.

The modern stuff, in contrast, is far more tolerant of differing production environments. All of the deadly stuff is in another room (no worries about using insufficient formalin or not heating long enough) and the genetics are exceedingly well defined with no dangerous introns anywhere in the genome (unlike a lot of attenuated viruses where you are just a couple of single nucleotide mutations away from restoring ORFs).

None of this is to say that either traditional vaccine type is particularly dangerous compared to actually getting the disease in question (nor is it even when weighting low likelihood of infection against adverse vaccine events). We replaced the Sabin polio vaccine (live) with the Salk vaccine (inactivated) in the US out of safety concerns, but it was only a 1/50,000 or so difference.

As is, stuff like HPV have far fewer reported adverse events and I suspect that the virus-like particles and other component strategies will become the default option for future vaccine efforts.

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satire/not satire?
"professor Jesse Goldberg, who will teach “African American & American Literature and Composition” at Auburn University, took to social media to proclaim, “fuck every single cop,” before urging police officers to “refuse to do their job and quit.”

Not Satire: https://www.wrbl.com/news/auburn-university-condemns-au-lecturers-anti-police-social-media-posts/
(And would someone tell Auburn's Public Safety Director the word is faze, not phase in this sense.)

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This has fuckall to do with vaccines, hun.

bullshit
the university is where peeps are trained to make vaccines.
fubar the university
you gonna fubar the vaccines, hun

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So a vaccine designed to target a particular virus's weakness would never, ever result in another strain gaining a foothold.

Shh - don't mention influenza.

We just design another based on whatever new AB we create in our bodies to fight off the new strain.

Welcome to influenza - except due to the lead time of manufacturing hundreds of millions of doses, we have to guess which strain will be wide spread.

It turns out the problem is not in designing, it is in the guessing. Or predicting, or forecasting - whichever term sounds appropriate.

Now prior_approval can explain to the class the difference in mutation rates between influenza and corona.

How? SARS-CoV-2 hasn't even been around for a year. What does SARS-CoV-2 have to do with the decades of experience related to creating and manufacturing influenza or HPV vaccines?

Corona-chan herself might be novel, but coronaviruses are certainly not.

What's the mutation rate of similar viruses compared to influenza? We have this information

Then why not post a link?

Posting a link to prior_approval trolling? What would even be the point?

https://www.livescience.com/coronavirus-mutation-rate.html

https://bmcevolbiol.biomedcentral.com/articles/10.1186/1471-2148-4-21

https://www.the-scientist.com/news-opinion/relatively-stable-sars-cov-2-genome-is-good-news-for-a-vaccine-67319

The first link only talks about 'seasonal' flu, which is likely referring to influenza A, not influenza B. It would appear that influenza B and SARS-CoV2 have roughly the same mutation rate. And influenza B mutates enough that lasting immunity is not possible.

The third link seems a bit dated in terms of what we have learned about SARS-CoV2 immunity since the end of May.

Thanks for the links.

Based on genomic sampling over time, the substitution rate is estimated to be 0.00084 per site per year (www.nextstrain.org; [8]; 16 May 2020), 2- to 6-fold lower than the substitution rate for influenza (0.004-0.005 subst/site/yr for influenza A and 0.002 subst/site/yr
4for influenza B [9]).

It's not the same as Influenza B

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With newer technologies and changing viruses, the changing natural AB will be identified and then the man made will be redone based on that.

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All RNA viruses mutate fast because their RNA dependent RNA polymerase (RdRP), the enzyme that catalyzes the RNA strand complimentary to the virus’ genome RNA doesn’t have a proof reading mechanism. 1 in 10^3 to 1 in 10^5 of the nucleotides synthesized are mis-incorporated
The Influenza A genome is 13.5 Kilobases long (kB), the Covid -19 genome is ~ 30 kB, so there should be more mutations per generation of Covid-19 than per generation of Influenza A ?
No, because the SARs-CoV-2 RdRP has a proof reading mechanism similar to the one for DNA polymerase. It’s an exonuclease site ( NSP14= non structural protein 14) that looks like a half open hand. When the wrong base shows up, the polymerase pauses and the incorrect base gets transferred from the “fingers” to the “palm” from the 3’ -> 5’ exonuclease site, 3nm away where it’s kicked out, then the 3’ end flips back into the polymerase site where the correct base can be inserted.

Without this proof reading mechanism, a 30 kB RNA genome would have too many mutations and would not be viable across generations.

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There's a new Lyme vaccine for humans. Great news for hikers.

Indeed that's a good development , but it says "could be available by 2025".
I guess if it's not for Covid-19 we're stuck with the very slow development cycles.

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~ 50,000 men, women and children die EVERY day from infectious diseases worldwide (not counting Covid-19) .

Vaccines have a long way to go.

Top infectious killers are:
HIV/AIDS Tuberculosis Pneumonia Infectious-Diarrhea Malaria

Certainly, but that is why treatment and prevention are also important. All of these are the subjects of prolonged public health campaigns but poverty and dysfunctional governments make the implementation of effective prevention and treatment policies difficult.

As for pneumonia, I haven't found a good answer on this but I wonder how many pneumonia deaths are really deaths from influenza which could have been prevented by more widespread flu vaccination. Ever since covid-19 started and people started quoting flu death figures from the CDC, it has been obvious that flu deaths are massively under-counted in official cause of death statistics. Yet there are tens of thousands of deaths in the U.S. every year that get classified as "pneumonia, unspecified."

They’re often commingled together depending on what the physician puts on the death certificate or whether there was an influenza test performed. Pneumonia however occurs all year round whereas the flu disappears in the summer.
~ 1/3 of pneumonia cases come from viruses that cause colds or the flu ( Influenza, RSV, adenovirus ...). You can start with the flu, get viral pneumonia and/or perhaps acquire bacterial pneumonia due to a weakened immune system. Some of these bacterial infections are acquired in hospitals.
So that’s the problem. Starting with influenza, you can branch into viral or bacterial pneumonia and what should be listed on the death certificate is not entirely clear.

"what should be listed on the death certificate is not entirely clear." Which is why the notion of a 'true' number of deaths from Covid-19 is a will-o'-the-wisp.

EVERYONE coming into the ER/hospital with suspected respiratory Covid 19 will also get tested for influenza. Some patients have had both, and then the clinician will have to decide on the relative diagnoses and the best course of treatment. Bacterial pneumonia is typically a different medical animal. Of course patients with either respiratory Covid 19 or Influenza are susceptible to secondary bacterial pneumonias.

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The "good news" here is COVID-19 is killing so many people it will be possible to make a reasonably close estimate.

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Progress is being made. HIV is very unusual because it's the fastest mutating biological entity and because it can be latent until reactivated ( so it hides in cells DNA ( CD4 T cells) and stays out of reach).
Some new strategies are trying to awaken these dormant HIV and flush the virus for complete elimination

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Tabarrok is forgiven, just this once, for a Straussian blog post. Just this once, and only because lives are at stake. If half or more of Americans refuse to take the vaccine, it will confirm my concerns. I hope I am wrong, and that Americans are smarter than Tabarrok gives them credit for. A given number will have negative reactions to the vaccine. That's the case with all vaccines. And when it happens, the "secret" will be exposed, at which point herd immunity will only occur through natural selection.

Herd immunity already happened in Sweden.

Not in Sweden. It is a bit more defensible to talk about several cities, but even there, the term herd immunity seems unsupported by current data..

" That's according to medical technology company Werlabs, which analysed 83,000 tests in Stockholm, Gothenburg and Malmö.

Across all the tests, 14.4 percent showed a positive result, meaning the person tested had developed the antibody to fight against coronavirus and believed to protect against re-infection for at least a few months. Individuals can choose to do the tests, meaning that these 83,000 are not a representative sample even of these three cities." www.thelocal.se/20200723/14-of-antibody-tests-positive-in-sweden

For better or worse we know that immune individuals won’t necessarily show positive in antibody tests.

The real test will be which countries succumb to new waves when they reopen.

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There's likely some herd immunity going on in the big cities, otherwise you have to explain why the cases and deaths are way down .
There are also other factors . Herd immunity most likely occurs at lower values than the classical SIR model predicts , because of heterogeneity ( susceptibility varies across the population, see recent papers posted by Tyler this week ( Gomes, Tkatchenko ) and this lowers the herd immunity threshold significantly ) and some percentage of the population is probably quasi immune ( T cell results on cross reactivity with other HCoVs)

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It was only a few days ago that 25 Swedish doctors and scientists made this statement.

You can argue whether the Swedish course was the wise one, but they did achieve some kind of herd immunity in the big cities as evidenced by the plunging case and death rates. Also antibodies may not be that detectable after a while depending on test sensitivity but protection is still there. ( see the Akiko Iwasaki NY times article today posted by Alex)

I am going to make an analogy that I know is unfair, but it captures a bit of what I feel about the Sweden course:

"My solution to rising commute times is that some of us go stand in traffic."

I mean sure, it works. You can "go back to normal" afterward. It's just not super moral.

Too early to tell if they made a wise decision regarding not locking down the country.

We'll see what their excess deaths looks like for the whole of 2020 compared to the rest of Europe, as well as the total economic impact

Apparently Sweden is the only economy to have gained any ground in 2020.

https://www.cnbc.com/2020/05/29/coronavirus-swedens-gdp-actually-grew-in-the-first-quarter.html

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It's going to be fascinating watching all the people who insist that "any virus risk above zero is unacceptable and evil" turning around and telling people "shut up and take your vaccine; so what if some people are harmed."

Are you vaccine free, Tom?

Or did you in fact take your vaccines for exactly these rational trade-offs?

Is that the doublethink that will be required? "Pretending that a new, rushed vaccine has the same risk profile as those that have been established over decades is rational; waiting for actual observation and science is crazy"?

The unspoken subtext here, of course, is "the same grocery workers who have been risking exposure to the virus in order to keep me safe better hurry up and risk exposure to vaccine side-effects to keep me safe." After a while that's got to start feeling a little dirty.

I don't think the idea that we take, for example the tetanus vaccine, is because the trade-offs look good is "double-think."

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For what it's worth, I could see myself getting a Lyme or COVID vaccine very early, for the same reason for both, that they strike me as very unpleasant diseases even when you do survive.

There will be millions of willing 'vacciners' around the world lining up day #1. HC workers, nursing home patients, advanced seniors and those with pre-existing diseases. Those reluctant will have a long time to wait and see and then reassess.

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COVID ranges from asymptomatic, to mild, to severe. There are what appear to be substantiated, but unquantified rumours of longer-term effects from COVID, but these may or may not persist. My guess is if there is a government fund available for prevalent condition, there will indeed be a lot of them. However, on average, COVID seems to be extremely mild.

I can't imagine taking a vaccine to avoid what will seem by that time to be a tiny risk - unless I am forced to at gunpoint, which do worry is the plan.

The thing people always forget about vaccines is it is not all about you. Vaccines are rarely 100% effective for a given person. Being vaccinated protects you but it also protects everyone around you, even those who have been vaccinated already. Some of those people may have compromised immune systems or, for whatever reason, may be prone to have a severe or fatal reaction to SARS-CoV-2.

Put differently, (near-)universal vaccination is like a cheat code that gets us herd immunity very quickly. Non-universal vaccination, depending on the effectiveness of the vaccine, may mean it will take longer to reach herd immunity and even previously vaccinated people may still be at risk of infection.

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tells & signals
if the judiciary penguin committee meeting is not satire
then why they work so hard to keep A.G.
Barr from finishing a sentence for 4hours
Something big is cooking

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Look, I don't disagree but you ... ought to acknowledge your own ignorance regarding the FDA and medical issues. Things are quite complicated in the medical space, and I can potentially come up with a number of reasons why you don't want too inaccurate tests on the market.

I agree that medical professionals and regulators at the FDA doing know enough about economic effects of their indecision. But it should be noted that you, in turn, have little knowledge about medicine.

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HPV vaccine triggers an almost 100% immune response from "conservatives."

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Amazing article, keep it up

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