Developing the Covid-19 vaccine

[jdc]

Moderna's vaccine against the SA strain sent to NIH for trials: https://www.ft.com/content/a14a91b1-8ce ... 2bada4f50b 'Fauci’s team at the NIH will begin testing it in phase 1 trial participants within weeks'

And: 'Moderna is also creating the first multivalent vaccine, which includes the genetic code for the spike protein of both the original strain of the virus and the 501.V2 variant, in hopes of making it effective against both variants.'

[Herainestold]

America approves the one dose J&J vax, on a weekend no less. They still have not approved AZ, waiting for the results of their US trial.

https://www.bbc.com/news/world-us-canada-56226979

[gosling]

Novavax is confident that they'll get UK approval for their vaccine in March, and is going to change their trial protocol as a result. I should get my placebo/vaccine dose in April:
https://www.chelwest.nhs.uk/about-us/re ... s-feb-2021

[Herainestold]

I am just thinking that it is amazing that we have so many vaccines that all seem to work. We haven't had much luck with anti-virals or other treatment drugs, at least not yet, but the vaccines look like they are a huge success.

[jdc]

I am just thinking that it is amazing that we have so many vaccines that all seem to work. We haven't had much luck with anti-virals or other treatment drugs, at least not yet, but the vaccines look like they are a huge success.

It's a pretty decent success rate so far. NYT tracker has it at 6 approved, 6 in limited/early use, and 4 abandoned after trials (plus the 87 still in trials that we don't know about yet).

[bob sterman]

Even with highly effective vaccines available - the "Great Bullsh*ttington" types won't stop.

A "Retired pediatrician" reckons he's calculated a Number Needed to Treat for the Pfizer-BioNTech based on the data from Israel, doesn't like the look of it, and is advocating...

"Some of us believe that vaccination should be targeted at the ~20% of the population that is truly high risk, and let the rest of the population acquire broader and more lasting protection from natural infection, an approach that may be safer and more cost-effective overall"

https://www.bmj.com/content/372/bmj.n56 ... -responses

The stupid is so strong in his "response" I can't be bothered to check whether the NNT calculation is correct - but even if it is, it's the NNT to get a benefit during a 42 day period! I would imagine most vaccine recipients were hoping to enjoy benefits over a longer period than this.

And this idea that natural infection is a safer approach for acquiring immunity - how about we compare the IFR for natural infections vs vaccines. Perhaps call it the NNK (Number Needed to Kill).

The frustrating thing is the anti-vaxxers will refer to his comment on an editorial as an "article in the BMJ".

[shpalman]

Pfizer vaccine may be less effective in people with obesity

Italian researchers have discovered that healthcare workers with obesity produced only about half the amount of antibodies in response to a second dose of the jab compared with healthy people. Although it is too soon to know what this means for the efficacy of the vaccine, it might imply that people with obesity need an additional booster dose to ensure they are adequately protected against coronavirus.

Previous research has suggested that obesity – which is defined as having a body mass index (BMI) over 30 – increases the risk of dying of Covid-19 by nearly 50%, as well as increasing the risk of ending up in hospital by 113%.

Non-peer-reviewed preprint at https://www.medrxiv.org/content/10.1101 ... 21251664v1

[Herainestold]

Pfizer vaccine may be less effective in people with obesity

Italian researchers have discovered that healthcare workers with obesity produced only about half the amount of antibodies in response to a second dose of the jab compared with healthy people. Although it is too soon to know what this means for the efficacy of the vaccine, it might imply that people with obesity need an additional booster dose to ensure they are adequately protected against coronavirus.

Previous research has suggested that obesity – which is defined as having a body mass index (BMI) over 30 – increases the risk of dying of Covid-19 by nearly 50%, as well as increasing the risk of ending up in hospital by 113%.

Non-peer-reviewed preprint at https://www.medrxiv.org/content/10.1101 ... 21251664v1

This is what I have been wondering about. I read that the Moderna jab has more active ingredient per dose, yet produces a similar result to Pfizer.
Maybe Moderna should be randomized against Pfizer in obese people.

[Herainestold]

Even with highly effective vaccines available - the "Great Bullsh*ttington" types won't stop.

A "Retired pediatrician" reckons he's calculated a Number Needed to Treat for the Pfizer-BioNTech based on the data from Israel, doesn't like the look of it, and is advocating...

"Some of us believe that vaccination should be targeted at the ~20% of the population that is truly high risk, and let the rest of the population acquire broader and more lasting protection from natural infection, an approach that may be safer and more cost-effective overall"

https://www.bmj.com/content/372/bmj.n56 ... -responses

The stupid is so strong in his "response" I can't be bothered to check whether the NNT calculation is correct - but even if it is, it's the NNT to get a benefit during a 42 day period! I would imagine most vaccine recipients were hoping to enjoy benefits over a longer period than this.

And this idea that natural infection is a safer approach for acquiring immunity - how about we compare the IFR for natural infections vs vaccines. Perhaps call it the NNK (Number Needed to Kill).

The frustrating thing is the anti-vaxxers will refer to his comment on an editorial as an "article in the BMJ".

I thought I read somewhere that the vaccination gives a more longer lasting superior immunization response than natural infection. I might be wrong.
In any case it seems like a dumb response. Vaccinate everybody!
`

[shpalman]

Belgium is also considering giving the AstraZeneca vaccine to over-55's after all https://www.theguardian.com/world/2021/ ... r-over-55s

[Woodchopper]

Reanalysis of the Pfizer mRNA BNT162b2 SARS-CoV-2 vaccine data fails to find any increased efficacy following the boost: Implications for vaccination policy and our understanding of the mode of action

Strongly protective immunity develops rapidly following a single vaccination and at least in the short period covered by the timetable of the Phase III trial, there was no additional benefit from a second vaccination. This increases options for use of this vaccine, e.g., for ring fence vaccination, for use in travelers and for mass vaccination rollout. It highlights the need for further research into duration of immunity following a single vaccination and for understanding mechanisms of protection.

https://www.medrxiv.org/content/10.1101 ... 21252315v1

[Millennie Al]

Pfizer vaccine may be less effective in people with obesity

Non-peer-reviewed preprint at https://www.medrxiv.org/content/10.1101 ... 21251664v1

Maybe it just means that the existing dose is inadequate (i.e. not that an additional separate dose is required). There are many treatments which are calibrated by body weight.

[shpalman]

Pfizer vaccine may be less effective in people with obesity

Non-peer-reviewed preprint at https://www.medrxiv.org/content/10.1101 ... 21251664v1

Maybe it just means that the existing dose is inadequate (i.e. not that an additional separate dose is required). There are many treatments which are calibrated by body weight.

Does that also mean they should need a higher viral load in order to get infected?

[Woodchopper]

COVID-19 Vaccine Tracker
https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/

There are others but this one is pretty comprehensive. Here’s a write up: https://www.thelancet.com/journals/lang ... 7/fulltext

[Millennie Al]

Pfizer vaccine may be less effective in people with obesity

Non-peer-reviewed preprint at https://www.medrxiv.org/content/10.1101 ... 21251664v1

Maybe it just means that the existing dose is inadequate (i.e. not that an additional separate dose is required). There are many treatments which are calibrated by body weight.

Does that also mean they should need a higher viral load in order to get infected?

An interesting question, but I think the answer is no - on the grounds that the virus reproduces but the vaccine doesn't. It may mean that it takes slightly longer from exposure to symptoms for heavier people, but whether that's noticeable or not will depend on how long it takes the virus to double its quantity.

[lpm]

The vaccine doesn't reproduce but the immune system thingies do.

Does a heavy person have fewer B cells proportionately or the same? Is the dose effectively diluted?

I'd have thought we all have the same quantity of immune system. If a 10 stone person has 100 immune system points, wouldn't they stay at 100 points if they put on weight to 15 stone? Not go to 150 points. The dose of vaccine at 10 stone would trigger those 100 points, same dose would trigger the same at 15 stone.

[headshot]

Question from a Luddite:

Is there a difference between becoming infected via respiratory tracts compared to being vaccinated into the bloodstream?

Is there something about the blood makeup of obese people, or the way the vaccine is absorbed, compared to a virus entering via the respiratory tract and multiplying there?

[shpalman]

Why should there be a difference? The whole point of this paper is that we know COVID-19 is more severe in obese individuals

Since obesity is a major risk factor for morbidity and mortality for patients with COVID-19(Popkin BM, D. S, Green WD, Beck MA, Algaith T, Herbst CH, et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obes Rev. 2020;21(11):e13128), it is mandatory to plan an efficient vaccination program in this subgroup. Evidence suggests that SARS-CoV-2 infections are more severe and linger for about five days longer in people who are obese than in those who are lean(Drucker DJ. Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning. Cell Metab. 2021).

so it's important to figure out if the vaccine is also less effective in them (which turns out to be the case, at least for the endpoints measured in the paper).

It may not necessarily be because

The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells(Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17(2):179–88).

but it's a better mechanism than "there's more of an obese person so it's harder for their immune system to cover all of it" and there's no need to postulate differences between the infection and the vaccine because they are developing less immune response to both.

[basementer]

The vaccine doesn't reproduce but the immune system thingies do.

My understanding is that the mRNA vaccine does reproduce. It's more like a conventional attenuated vaccine than an inactivated one: first it subverts the body into producing millions of blank newspaper articles labelled "Daily Mail", then over the next two or three weeks the immune system learns to destroy anything carrying that logo. After that, if exposed to real Mail articles, the immune response will be to turn on the shredder.

[shpalman]

The vaccine doesn't reproduce but the immune system thingies do.

My understanding is that the mRNA vaccine does reproduce. It's more like a conventional attenuated vaccine than an inactivated one: first it subverts the body into producing millions of blank newspaper articles labelled "Daily Mail", then over the next two or three weeks the immune system learns to destroy anything carrying that logo. After that, if exposed to real Mail articles, the immune response will be to turn on the shredder.

A virus gets a host cell to make more copies of the virus which can then infect other host cells.

I think the mRNA vaccine particles each get into a host cell where the mRNA gets the host cell to make spike proteins, which then can't go on to infect other cells.

The viral-vector ones just use a virus to get the mRNA into a host cell to make spike proteins but again then viral vector itself doesn't reproduce in humans for some reason. AstraZeneca uses a chimp adenovirus for example.

[Herainestold]

The vaccine doesn't reproduce but the immune system thingies do.

My understanding is that the mRNA vaccine does reproduce. It's more like a conventional attenuated vaccine than an inactivated one: first it subverts the body into producing millions of blank newspaper articles labelled "Daily Mail", then over the next two or three weeks the immune system learns to destroy anything carrying that logo. After that, if exposed to real Mail articles, the immune response will be to turn on the shredder.

That is a good analogy, even I can understand it. How accurate is it?

[Herainestold]

Why should there be a difference? The whole point of this paper is that we know COVID-19 is more severe in obese individuals

Since obesity is a major risk factor for morbidity and mortality for patients with COVID-19(Popkin BM, D. S, Green WD, Beck MA, Algaith T, Herbst CH, et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obes Rev. 2020;21(11):e13128), it is mandatory to plan an efficient vaccination program in this subgroup. Evidence suggests that SARS-CoV-2 infections are more severe and linger for about five days longer in people who are obese than in those who are lean(Drucker DJ. Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning. Cell Metab. 2021).

so it's important to figure out if the vaccine is also less effective in them (which turns out to be the case, at least for the endpoints measured in the paper).

It may not necessarily be because

The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells(Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17(2):179–88).

but it's a better mechanism than "there's more of an obese person so it's harder for their immune system to cover all of it" and there's no need to postulate differences between the infection and the vaccine because they are developing less immune response to both.

So why is COVID-19 more severe in POC and BAME individuals? Do we know?

[shpalman]

So why is COVID-19 more severe in POC and BAME individuals? Do we know?

We don't know.

German doctors broach ‘taboo’ subject of Covid toll on minority groups

Lothar Wieler, the head of the Robert Koch Institute, Germany’s disease control agency, has been quoted by German media as saying the topic was “taboo” for the German government who feared the debate could be seen as racist. He reportedly called it a “huge problem” that had “massive implications” for the government.

...

There has been very little public debate in Germany about the extent to which people from minority ethnic groups might be affected more by the virus, whether owing to not being reached by government communications on the virus, or to a higher risk of exposure through work, or to other reasons such as health issues or living arrangements.

[Woodchopper]

So why is COVID-19 more severe in POC and BAME individuals? Do we know?

You can find some answers here: https://assets.publishing.service.gov.u ... r_2020.pdf

In short, severity is affected by their jobs, housing, members of the household and health conditions before they contracted COVID-19. But those factors don't explain all the disparities.

[JQH]

So why is COVID-19 more severe in POC and BAME individuals? Do we know?

The question to be asked is "Why do people of colour have worse health outcomes across the board than whites?" This problem is not covid specific