nortex97 said:

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We've never had a coronavirus vaccine and for a virus that tends to rapidly mutate (such as influenza) I'd be shocked if we ever have one that lasts more than 12-18 months.

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1) COVID doesn't mutate as rapidly as influenza.
2) we have a new flu vaccine every year because there are hundreds of influenza viruses and the vaccine only protects against the 3-4 they think are going to be big this year. Because of the nature of influenzas, next years dominant strains are different.
3) influenza vaccine targets highly variable regions whereas the coronavirus vaccines target a fairly stable region based on genetic analysis of samples for many many patients.

There is literally nothing the same about the COVID vaccine and the flu vaccine.

BiochemAg97 said:

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nortex97 said:

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We've never had a coronavirus vaccine and for a virus that tends to rapidly mutate (such as influenza) I'd be shocked if we ever have one that lasts more than 12-18 months.

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1) COVID doesn't mutate as rapidly as influenza.
2) we have a new flu vaccine every year because there are hundreds of influenza viruses and the vaccine only protects against the 3-4 they think are going to be big this year. Because of the nature of influenzas, next years dominant strains are different.
3) influenza vaccine targets highly variable regions whereas the coronavirus vaccines target a fairly stable region based on genetic analysis of samples for many many patients.

There is literally nothing the same about the COVID vaccine and the flu vaccine.

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1. Not as fast but it does mutate fairly rapidly. Notice the new strain in Denmark. It's slower than 'most' mRNA viruses, but they do tend to be a very rapidly mutating group. It's rate of change is about half that of the flu. Enzymes that copy RNA are prone to errors and there's no 'check' mechanism. The D614G mutation in particular made it more infectious but I do believe also easier to target for a vaccine.
2. Yes. Influenza is a challenging quad cocktail they try to select annually.
3. Not sure the point here. You'll have to explain to me in plain english what portions of an RNA virus are stable vs. the rest.

We have something like 14-16 strains of the thing today. Realistically, we'll have at least double that number in a year (and more likely triple).

I realize vaccine development has been...problematic due to the lack of economic incentives for 'minor' viruses (SARS basically went away). My point is there has never been a coronavirus vaccine that has been developed/worked, and to look at the present state and assume a longer acting one will shortly exist a la hep B or HPV is not a sound analysis.

Long term, it's realistic China or another will release another problematic virus on the world again, and we need greater depth/breadth of vaccine development regardless of the present profit rationales for places like Pfizer etc.

notex said:

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BiochemAg97 said:

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nortex97 said:

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We've never had a coronavirus vaccine and for a virus that tends to rapidly mutate (such as influenza) I'd be shocked if we ever have one that lasts more than 12-18 months.

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1) COVID doesn't mutate as rapidly as influenza.
2) we have a new flu vaccine every year because there are hundreds of influenza viruses and the vaccine only protects against the 3-4 they think are going to be big this year. Because of the nature of influenzas, next years dominant strains are different.
3) influenza vaccine targets highly variable regions whereas the coronavirus vaccines target a fairly stable region based on genetic analysis of samples for many many patients.

There is literally nothing the same about the COVID vaccine and the flu vaccine.

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1. Not as fast but it does mutate fairly rapidly. Notice the new strain in Denmark. It's slower than 'most' mRNA viruses, but they do tend to be a very rapidly mutating group. It's rate of change is about half that of the flu. Enzymes that copy RNA are prone to errors and there's no 'check' mechanism. The D614G mutation in particular made it more infectious but I do believe also easier to target for a vaccine.
2. Yes. Influenza is a challenging quad cocktail they try to select annually.
3. Not sure the point here. You'll have to explain to me in plain english what portions of an RNA virus are stable vs. the rest.

We have something like 14-16 strains of the thing today. Realistically, we'll have at least double that number in a year (and more likely triple).

I realize vaccine development has been...problematic due to the lack of economic incentives for 'minor' viruses (SARS basically went away). My point is there has never been a coronavirus vaccine that has been developed/worked, and to look at the present state and assume a longer acting one will shortly exist a la hep B or HPV is not a sound analysis.

Long term, it's realistic China or another will release another problematic virus on the world again, and we need greater depth/breadth of vaccine development regardless of the present profit rationales for places like Pfizer etc.

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It depends on what part of the virus the vaccine targets. The COVID mRNA vaccines target the "spike protein" that is stable and required for it to thrive. The Flu vaccine targets the whole entire capsule which is very shifty.

Completely different virus, completely different vaccines.

Sure but the spike protein is precisely what suddenly changed. I believe the D614G mutation happened around Jan-February (certainly by March). It could certainly change again, and if it does, it will have unknown consequences on the efficacy of any/all vaccines...

Quote:

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Compared with HIV, SARS-CoV-2 is changing much more slowly as it spreads. But one mutation stood out to Korber. It was in the gene encoding the spike protein, which helps virus particles to penetrate cells. Korber saw the mutation appearing again and again in samples from people with COVID-19. At the 614th amino-acid position of the spike protein, the amino acid aspartate (D, in biochemical shorthand) was regularly being replaced by glycine (G) because of a copying fault that altered a single nucleotide in the virus's 29,903-letter RNA code. Virologists were calling it the D614G mutation.

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Quote:

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The Baltimore classification of viruses establishes the following categories according to the genetic material contained in the virion:

• positive-strand RNA viruses (e.g., rhinoviruses, hepatitis C virus, noroviruses, tobacco mosaic virus),
• negative-strand RNA viruses (influenza viruses, Ebola virus, rabies virus),
• double-strand RNA viruses (rotaviruses, bursal disease virus), retroviruses (HIV, human T cell leukemia virus), para-retroviruses (hepatitis B viruses),
• single-stranded DNA viruses (parvoviruses, bacterio****e X174), and
• double-stranded DNA viruses (papillomaviruses, herpesviruses, adenoviruses, poxviruses).

Viruses are the biological systems with the widest variation in mutation rates, the largest differences being found between RNA and DNA viruses.

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Covid/coronaviruses are positive-strand RNA. I think we could agree that positive-strand RNA viruses do mutate relatively rapidly. Further, mutation rates are often related to the spectrum of genetic diversity of the hosts; since COVID19 is functionally a global virus now, a growing mutation rate should be anticipated.

notex said:

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BiochemAg97 said:

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nortex97 said:

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We've never had a coronavirus vaccine and for a virus that tends to rapidly mutate (such as influenza) I'd be shocked if we ever have one that lasts more than 12-18 months.

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1) COVID doesn't mutate as rapidly as influenza.
2) we have a new flu vaccine every year because there are hundreds of influenza viruses and the vaccine only protects against the 3-4 they think are going to be big this year. Because of the nature of influenzas, next years dominant strains are different.
3) influenza vaccine targets highly variable regions whereas the coronavirus vaccines target a fairly stable region based on genetic analysis of samples for many many patients.

There is literally nothing the same about the COVID vaccine and the flu vaccine.

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1. Not as fast but it does mutate fairly rapidly. Notice the new strain in Denmark. It's slower than 'most' mRNA viruses, but they do tend to be a very rapidly mutating group. It's rate of change is about half that of the flu. Enzymes that copy RNA are prone to errors and there's no 'check' mechanism. The D614G mutation in particular made it more infectious but I do believe also easier to target for a vaccine.
2. Yes. Influenza is a challenging quad cocktail they try to select annually.
3. Not sure the point here. You'll have to explain to me in plain english what portions of an RNA virus are stable vs. the rest.

We have something like 14-16 strains of the thing today. Realistically, we'll have at least double that number in a year (and more likely triple).

I realize vaccine development has been...problematic due to the lack of economic incentives for 'minor' viruses (SARS basically went away). My point is there has never been a coronavirus vaccine that has been developed/worked, and to look at the present state and assume a longer acting one will shortly exist a la hep B or HPV is not a sound analysis.

Long term, it's realistic China or another will release another problematic virus on the world again, and we need greater depth/breadth of vaccine development regardless of the present profit rationales for places like Pfizer etc.

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There is selective pressure to maintain certain parts of the genome. Particularly relevant is the spike protein which is targeted by the vaccines. Portions that are necessary for insertion into a cell such as the receptor binding domain and parts involved in the conformational change that injects the viral genome into the cell once bound are slow to change. While the mutation rate is the same (it is random after all), a mutation that can't bind the ACE2 receptor or can't inject into the cell doesn't get replicated so doesn't become a strain. Mutations tend to accumulate in other parts of the genome where the change doesn't break the virus.

Not sure about your guess at how many strains in a year. We are already a year into COVID so I assume you mean this time next year. However, COVID mutation requires passage through multiple people. Infecting millions of people in a year means millions of opportunities to mutate. With a vaccine where most are immune, there would be far fewer infected people thus lowering the rate at which new strains evolve.

Agree completely that long term there is likely another coronavirus out there that makes the leap from animal to human. Given SARS, MERS, and COVID19, we are currently at a rate of once every 5-10 years. However with an adaptable platform like the mRNA vaccines, we could easily modify a vaccine to target the next one and ramp production in a matter of months, assuming we treat it like we do the flu vaccine where we don't require months/years of safety testing for each new version.

notex said:

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Sure but the spike protein is precisely what suddenly changed. I believe the D614G mutation happened around Jan-February (certainly by March). It could certainly change again, and if it does, it will have unknown consequences on the efficacy of any/all vaccines...

Quote:

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Compared with HIV, SARS-CoV-2 is changing much more slowly as it spreads. But one mutation stood out to Korber. It was in the gene encoding the spike protein, which helps virus particles to penetrate cells. Korber saw the mutation appearing again and again in samples from people with COVID-19. At the 614th amino-acid position of the spike protein, the amino acid aspartate (D, in biochemical shorthand) was regularly being replaced by glycine (G) because of a copying fault that altered a single nucleotide in the virus's 29,903-letter RNA code. Virologists were calling it the D614G mutation.

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https://www.nature.com/articles/s41401-020-0485-4/figures/2

[url=https://www.nature.com/articles/s41401-020-0485-4/figures/2][/url]There are parts of spike that can change without significantly effecting the function or shape of spike. Position 614 appears to be in one of those regions. RBD is 319 to 541. FP (fusion peptide which is involved in the insertion process) is from 788 to 806. 614 is in the middle of the region between these two functional domains and doesn't have an assigned function. It is likely some portion of the amino acids in that region are structurally significant, but a D to G mutation simply removes the side chain. D is a relatively small charged group and so losing that may have a small effect on the stability of the protein or alter a small patch of the surface in some way but isn't likely to leave a gaping hole in the hydrophobic core or create some steric hindrance that would blow the protein apart. Which all makes sense since D614G still works.

I haven't seen where mRNA-1273 maps to on the spike protein. Moderna's patents probably won't publish for another 6 months or so. Similar issues for Pfizer. Further antibodies would target epitopes, relatively small surface regions of the spike protein. When injected with a vaccine, the body creates antibodies to many epitopes on the surface on the protein. It is possible that D614G would effect an epitope if it altered a surface charge, although + to neutral is less of a change than + to -. If the antibody had a complementary - change in that spot, you end up with a weaker binding for the G variant, but it could still work. That might diminish the binding of one antibody, but you likely end up with antibodies to lots of other epitopes, some of which can't change very much and still have a functional virus. And it doesn't even matter if mRNA-1273 doesn't include D614.

For flu, you aren't looking at a few single amino acid changes when you switch from say H1N1 (2009 swine flu) to say H7N9 (2017 bird flu). Those are whole glycoproteins that are getting swapped out. And even with influenza mutating 2x faster than coronavirus, you don't need to make a new H1N1 vaccine each year. They swap out the H1N1 for something else, knowing that the people who got the prior shot with H1N1 and those who were infected are all immune to the circulating H1N1 the next year, thus making H1N1 much less likely to be one of the dominate s flu strains. Big difference between the flu and covid vaccines.

notex said:

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BiochemAg97 said:

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nortex97 said:

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We've never had a coronavirus vaccine and for a virus that tends to rapidly mutate (such as influenza) I'd be shocked if we ever have one that lasts more than 12-18 months.

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1) COVID doesn't mutate as rapidly as influenza.
2) we have a new flu vaccine every year because there are hundreds of influenza viruses and the vaccine only protects against the 3-4 they think are going to be big this year. Because of the nature of influenzas, next years dominant strains are different.
3) influenza vaccine targets highly variable regions whereas the coronavirus vaccines target a fairly stable region based on genetic analysis of samples for many many patients.

There is literally nothing the same about the COVID vaccine and the flu vaccine.

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1. Not as fast but it does mutate fairly rapidly. Notice the new strain in Denmark. It's slower than 'most' mRNA viruses, but they do tend to be a very rapidly mutating group. It's rate of change is about half that of the flu. Enzymes that copy RNA are prone to errors and there's no 'check' mechanism. The D614G mutation in particular made it more infectious but I do believe also easier to target for a vaccine.

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The "new strain" in Denmark is special. Assuming it is actually a COVID-19 variant and not another zoonotic coronavirus that made the jump from animal to human, it involved a jump from human to mink and then transmission back. And here is the key part. Mink aren't human so the ACE2 receptor in mink is a bit different from the ACE2 receptor in humans. Once in mink, there can be selection to adapt the RBD of spike to better fit mink ACE2, but obviously still close enough to fit human because it came back and infected some humans. Now you have a change that MIGHT alter the effect of the vaccine. They don't know this, it was just a concern of Denmark.