Developing the Covid-19 vaccine

[jimbob]

https://www.cdc.gov/mmwr/volumes/70/wr/ ... mm7044e1_w

Summary
What is already known about this topic?

Previous infection with SARS-CoV-2 or COVID-19 vaccination can provide immunity and protection against subsequent SARS-CoV-2 infection and illness.

What is added by this report?

Among COVID-19–like illness hospitalizations among adults aged ≥18 years whose previous infection or vaccination occurred 90–179 days earlier, the adjusted odds of laboratory-confirmed COVID-19 among unvaccinated adults with previous SARS-CoV-2 infection were 5.49-fold higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine who had no previous documented infection (95% confidence interval = 2.75–10.99).

What are the implications for public health practice?

All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2.

[shpalman]

Health secretary is not health regulator

The pharmaceutical firm Valneva has asked for an apology and has not ruled out future legal action after the British health secretary told MPs its coronavirus vaccine would not get approval for use in the UK, PA reports.

Javid originally told MPs the company['s vaccine] “would not get approval” by the regulator, but later amended Hansard, the official parliamentary record, to state the vaccine “has not yet gained” clearance approval #secondmentions.

[dyqik]

Health secretary is not health regulator

The pharmaceutical firm Valneva has asked for an apology and has not ruled out future legal action after the British health secretary told MPs its coronavirus vaccine would not get approval for use in the UK, PA reports.

Javid originally told MPs the company['s vaccine] “would not get approval” by the regulator, but later amended Hansard, the official parliamentary record, to state the vaccine “has not yet gained” clearance approval #secondmentions.

I wonder how much stock he bought in Valneva between the statement and correction. </cynicism>

[tom p]

Health secretary is not health regulator

The pharmaceutical firm Valneva has asked for an apology and has not ruled out future legal action after the British health secretary told MPs its coronavirus vaccine would not get approval for use in the UK, PA reports.

Javid originally told MPs the company['s vaccine] “would not get approval” by the regulator, but later amended Hansard, the official parliamentary record, to state the vaccine “has not yet gained” clearance approval #secondmentions.

He has parliamentary privilege, so I would be astonished if there were any legal action they could take against Javid personally. and since it was corrected, I expect there is nothing they could take against HMG.
also, technically the health secretary is the regulator - all GB marketing authorisations are signed by the heath secretary and they are not valid until he/she has done so.

[shpalman]

Health secretary is not health regulator

The pharmaceutical firm Valneva has asked for an apology and has not ruled out future legal action after the British health secretary told MPs its coronavirus vaccine would not get approval for use in the UK, PA reports.

Javid originally told MPs the company['s vaccine] “would not get approval” by the regulator, but later amended Hansard, the official parliamentary record, to state the vaccine “has not yet gained” clearance approval #secondmentions.

He has parliamentary privilege, so I would be astonished if there were any legal action they could take against Javid personally. and since it was corrected, I expect there is nothing they could take against HMG.
also, technically the health secretary is the regulator - all GB marketing authorisations are signed by the heath secretary and they are not valid until he/she has done so.

Ok but it's not like he personally reads all the trial data and makes the decision himself on his own is it?

[shpalman]

Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2

Swadling, L., Diniz, M.O., Schmidt, N.M. et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature (2021). https://doi.org/10.1038/s41586-021-04186-8

Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion.

Written about at https://www.bbc.com/news/health-59207466 and https://www.theguardian.com/world/2021/ ... inds-study

The work suggests that a subset of people already had memory T-cells from previous infections from other seasonal coronaviruses causing common colds, which protected them from Covid-19.

[Herainestold]

A new nasal covid vaccine looks promising and will soon start phase III trials.

COVID-19 nasal vaccine candidate by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD) in a live attenuated influenza virus (LAIV) vector.To date, all the approved COVID-19 vaccines are administered through traditional muscle injection, which is commonly limited for their ability to induce mucosal immunity and local immunity.

In contrast, several vaccine candidates intended for intranasal delivery elicit mucosal IgA and CD8+T cell-mediated immune responses in the respiratory tract as well as serum IgG responses, resulting in reduced virus replication and viral shedding in both the lungs and the nasal passages than intramuscular vaccination. Furthermore, they have shown potential in animal models and early phase clinical trials.

The authors of a new study, published on the bioRxiv* preprint server, constructed a

This LAIV-based vaccine not only has the potential to overcome the limitations of intramuscular vaccines but there is also evidence that it shows improved efficacy compared with that of an inactivated influenza vaccine (IIV).

The data from this study demonstrates the rapid (1 day), prolonged (9 months), and broad protection offered by this vaccine candidate against SARS-CoV-2 infection in animal models. It is also shown to be immunogenic and well-tolerated in Chinese adults. A phase III clinical trial for this will be initiated soon.

Conclusion

Several countries have vaccinated the majority of their populations, but COVID-19 breakthrough infections are occurring in the vaccinated groups.

Moreover, the majority of children are not yet vaccinated. As countries are now reopening their borders to international travelers and with the emergence of variants of concern, it is expected that COVID-19 transmission in specific sections of people will increase.

Considering the limitations of the traditional intramuscular vaccines concerning their ability to induce local immunity, it is imperative to continually develop different vaccine strategies in response to the evolving COVID-19 pandemic.

https://www.news-medical.net/news/20211 ... ector.aspx

[tom p]

Given how many people are already vaccinated, it's probably at least a year away from meaningful results, unless there's a big outbreak somewhere and they can get in quick with vast quantities of their vaccine ready to inoculate tens of thousands of people in a very short time.
And even then, so what? we already have loads of vaccines that are perfectly safe and are already in large-scale production. This is an exceedingly minor extra good thing

[jimbob]

Not a Covid-19 vaccine but a novel approach for an mRNA vaccine

A new thread in Nerd Lab

https://www.science.org/doi/10.1126/science.acx9658

neat idea

MRNA technology is now famous for delivering vaccines against COVID-19, and this week it achieved another distinction with an experimental Lyme preventive announced by the collaboration launched in Ireland. “It’s the first vaccine [intended for humans] against an infectious disease that does not target the pathogen,” Fikrig says. The mRNA vaccine, administered to guinea pigs, turned tick bites red and inflamed. The ticks fed poorly, fell off early, and often failed to transmit the Lyme-causing bacterium. Researchers hope the vaccine will one day work the same way in humans.
It’s “a beautiful study,” says Ruth Montgomery, a cellular immunologist at Yale who was not involved with the work. “Potentially a mechanism like this could be very important in a number of tick-borne diseases.”

[Herainestold]

Given how many people are already vaccinated, it's probably at least a year away from meaningful results, unless there's a big outbreak somewhere and they can get in quick with vast quantities of their vaccine ready to inoculate tens of thousands of people in a very short time.
And even then, so what? we already have loads of vaccines that are perfectly safe and are already in large-scale production. This is an exceedingly minor extra good thing

The thought is that a nasal vaccine would be better at reducing transmission. Which the existing vaccines are not so good at.
I don't know if that is the case or it is just hype. Seems that would be hard to prove in a trial, as the existing vaccines are pretty good in the time period after full vaccination, lasting for a few months, but efficacy against transmission declines fairly rapidly. So to test if this vaccine is more efficacious against transmission the trials would have to last a long time, six months to a year before you would see this effect.

[shpalman]

the Economist summarises efficacy against Delta.

[shpalman]

AstraZeneca chief links Europe’s Covid surge to firm's inability to test it properly in old people and failure to deliver anything like the quantities they said they would

[Herainestold]

AstraZeneca chief links Europe’s Covid surge to firm's inability to test it properly in old people and failure to deliver anything like the quantities they said they would

I don't think the evidence supports his position.

Prof Matthew Snape, of the University of Oxford, has compared antibody and T-cell responses in people receiving standard or mixed schedules of the Pfizer and AstraZeneca vaccines. Although his team found evidence that a single dose of AstraZeneca induced a better T-cell response, the response was very similar shortly after receiving two doses

“Intriguingly, the best T-cell responses seem to come if you give a first dose of the AstraZeneca vaccine followed by Pfizer,” he said.

I thought it was bad to mix doses.

[shpalman]

I thought it was bad to mix doses.

Why?

I don't think it's bad, it's just that we couldn't practically test all the possible combinations of vaccines at Phase III level.

[Herainestold]

I thought it was bad to mix doses.

Why?

I don't think it's bad, it's just that we couldn't practically test all the possible combinations of vaccines at Phase III level.

Well I know some jurisdictions will not accept mixed doses. The US CDC was advising against it, although they may have changed their advice.

[monkey]

I thought it was bad to mix doses.

Why?

I don't think it's bad, it's just that we couldn't practically test all the possible combinations of vaccines at Phase III level.

Well I know some jurisdictions will not accept mixed doses. The US CDC was advising against it, although they may have changed their advice.

I'm not sure what the advice was before I got my booster, but the CDC reckoned mixing was OK for No. 3 at that time, and as far as I know they still think that. They didn't have any advice on whether it was best to mix or not, only that it was fine to do so*. They don't recommend mixing for shots 1+2.

This doesn't apply to the the AZ jab, 'cos that's not been approved for anything, only Pfizer, Moderna and J+J round this way.

*ETA: I did have a choice whether to mix or not.

[shpalman]

I got my second dose of AZ in while the rule was still "oh well, you survived the first one so you'll probably be fine" but I know some of the students were delayed in getting their second doses while the AIFA thought about whether it would be better to give them an mRNA one instead. I don't remember what the outcome was, apart from the delay obviously. Also I don't remember if this created problems with the Green Pass or non-EU almost-equivalent.

[Herainestold]

Why?

I don't think it's bad, it's just that we couldn't practically test all the possible combinations of vaccines at Phase III level.

Well I know some jurisdictions will not accept mixed doses. The US CDC was advising against it, although they may have changed their advice.

I'm not sure what the advice was before I got my booster, but the CDC reckoned mixing was OK for No. 3 at that time, and as far as I know they still think that. They didn't have any advice on whether it was best to mix or not, only that it was fine to do so*. They don't recommend mixing for shots 1+2.

This doesn't apply to the the AZ jab, 'cos that's not been approved for anything, only Pfizer, Moderna and J+J round this way.

*ETA: I did have a choice whether to mix or not.

The quotation referred to the initial two doses and not the third booster dose.
Here is the CDC advice:

CDC does not recommend mixing products for a two dose primary vaccine series or an additional primary dose. If you received a Pfizer-BioNTech or Moderna COVID-19 vaccine, you should get the same product when you need a second shot or additional primary dose. However, mixing and matching COVID-19 vaccines is allowed for booster shots.

As America never approved AZ, AZ/mRNA vax combination was never a possibility. It was not accepted as an allowable vaccine for incoming travellers,
but I believe it is okay now. I don't know how widely used that combination was, but I think some EU jurisdictions were doing AZ/mRNA.

[shpalman]

I checked, and some students here did indeed receive Pzifer as a second dose despite surviving the first AstraZeneca dose, being of an age at which even the UK considered AZ to not be worth the risk.

Meanwhile the EMA approves Pfizer vaccine for children aged 5 to 11 so expect various national rollout strategies to be updated soon.

[Woodchopper]

It looks like we know why the AZ vaccine caused rare blood clotting problems.

Paper: https://www.science.org/doi/10.1126/sciadv.abl8213

BBC summary: https://www.bbc.com/news/health-59418123

[nezumi]

It looks like we know why the AZ vaccine caused rare blood clotting problems.

Paper: https://www.science.org/doi/10.1126/sciadv.abl8213

BBC summary: https://www.bbc.com/news/health-59418123

Blimey that's interesting. I would imagine that changing the vector would mean redesigning the entire vaccine (if I'm wrong, do tell). I wonder if there's a simple tweak they can do to remove the risk. I obviously don't know enough about vaccine design to say. I hope someone will be along to explain the implications shortly

[headshot]

It would certainly be helpful for developing countries. They’ll probably sell it off even cheaper given that richer nations no longer want it.

[shpalman]

It would certainly be helpful for developing countries. They’ll probably sell it off even cheaper given that richer nations no longer want it.

Where individuals expressed hesitancy, a common reason was to make reference to the inconsistent approaches to use of the Oxford AstraZeneca vaccine in the Global North. Specific comments often focused on the reactions to the blood clots as possible adverse events. To quote one of our participants: “Why would I want that damaged white-man product?” News travels fast and easily in a globalized world.

from https://www.scientificamerican.com/arti ... rtly-why1/

[headshot]

Yeah. I should have added a “facetious” tag to my post.

[raven]

Where individuals expressed hesitancy, a common reason was to make reference to the inconsistent approaches to use of the Oxford AstraZeneca vaccine in the Global North. Specific comments often focused on the reactions to the blood clots as possible adverse events. To quote one of our participants: “Why would I want that damaged white-man product?” News travels fast and easily in a globalized world.

Which is perfectly understandable. I'm surprised that we had such high uptake of AZ here really, given that fatal blood clots happened.

There's probably some interesting psychological research to be done on how perception of risk differs between countries during all this. I reckon we're all a bit less fatalistic about infectious disease in the Global North because we're far less used to burying children due to it. You get inured to risks you live with every day.