Possible vaccines/treatment(s) for Coronavirus

[2hats]

Moderna have commenced trials of their next COVID-19 vaccine, mRNA-1283, which can potentially be shipped and stored at standard refrigerator temperatures. This is a phase I study evaluating doses at 10 µg, 30 µg, and 100 µg, as a 2-dose series, 28 days apart, and a single dose at 100 µg to compare with the current, approved, two dose regimen of 100 µg of mRNA-1273.

First Participants Dosed in Phase 1 Study Evaluating mRNA-1283, Moderna’s Next Generation COVID-19 Vaccine | Moderna, Inc.

mRNA-1283 is being developed as a potential refrigerator stable mRNA vaccine that will facilitate easier distribution and administration by healthcare providers CAMBRIDGE, Mass. --(BUSINESS WIRE)--Mar. 15, 2021-- Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA)

investors.modernatx.com

 

[2hats]

Fake Sputnik V seized in Mexico, apparently destined for Honduras.

Fake batch of Sputnik V vaccine seized in Mexico, Russian wealth fund says

Authorities in Mexico have seized a batch of fake doses of Russia's Sputnik V vaccine, the Russian Direct Investment Fund, which is responsible for exports of the COVID-19 vaccine, said on Thursday.

www.reuters.com

 

[2hats]

Phase III trial of Medicago/GSK CovLP adjuvanted COVID-19 vaccine (2 dose regimen) about to commence. CoVLP is a (nicotine) plant-derived vaccine candidate using Coronavirus-Like-Particle technology featuring the recombinant spike glycoprotein.

Media | Medicago

Welcome to Medicago’s Media Room, where you can find our latest news, key facts, figures and background information.

www.medicago.com

 

[8ball]

Moderna have commenced trials of their next COVID-19 vaccine, mRNA-1283, which can potentially be shipped and stored at standard refrigerator temperatures. This is a phase I study evaluating doses at 10 µg, 30 µg, and 100 µg, as a 2-dose series, 28 days apart, and a single dose at 100 µg to compare with the current, approved, two dose regimen of 100 µg of mRNA-1273.

First Participants Dosed in Phase 1 Study Evaluating mRNA-1283, Moderna’s Next Generation COVID-19 Vaccine | Moderna, Inc.

mRNA-1283 is being developed as a potential refrigerator stable mRNA vaccine that will facilitate easier distribution and administration by healthcare providers CAMBRIDGE, Mass. --(BUSINESS WIRE)--Mar. 15, 2021-- Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA)

investors.modernatx.com

This is a lipid nanoparticle mRNA vaccine, isn't it?
Bit of a blow for Pfizer, I'd think...

 

[2hats]

This is a lipid nanoparticle mRNA vaccine, isn't it?
Bit of a blow for Pfizer, I'd think...

Both BNT162b2 and mRNA-1273 use lipid nanoparticles, to both protect the nucleic acid from degradation and then facilitate cell uptake followed by release into the cytoplasm.

 

[8ball]

Uh... yeah.

 

[Doodler]

A case of the virus seen mutating in a patient with a compromised immune system:

"During the patient’s stay, 23 viral samples were available for analysis, the majority from his nose and throat. Between days 66 and 82, following the first two administrations of plasma, the team saw a dramatic shift in the virus population, with the mutated virus becoming dominant. Although this variant initially appeared to die away, it re-emerged again when the third course of remdesivir and convalescent plasma therapy were administered.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease, who led the research, said: “What we were seeing was essentially a competition between different variants of the virus, and we think it was driven by the convalescent plasma therapy. “The [mutated] virus that eventually won out...initially gained the upper hand during convalescent plasma therapy before being overtaken by other strains, but re-emerged when the therapy was resumed. One of the mutations is in the new UK variant, though there is no suggestion that our patient was where they first arose.”

He added: “Given that both vaccines and therapeutics are aimed at the spike protein, which we saw mutate in our patient, our study raises the worrying possibility that the virus could mutate to outwit our vaccines. This effect is unlikely to occur in patients with functioning immune systems, where viral diversity is likely to be lower due to better immune control. But it highlights the care we need to take when treating immunocompromised patients, where prolonged viral replication can occur, giving greater opportunity for the virus to mutate.”"

Coronavirus more likely to mutate into Kent strain in chronic infections

The Cambridge University scientists were the first to observe a Kent strain-like mutation happen in real time

www.cambridge-news.co.uk

Not surprising, iirc increased viral mutation rates have been observed in cats with Feline Immunodeficiency Syndrome. This has been known about for a while.

 

[8ball]

Not surprising, iirc increased viral mutation rates have been observed in cats with Feline Immunodeficiency Syndrome. This has been known about for a while.

Not sure what you mean by "increased" here. Increased from what?
In any case, FIV mutates quite a good bit faster than SARS-CoV-2.

The interesting bit (to me) is the almost real-time evolution of the virus in response to a therapy within a single (albeit immunocompromised) patient. Not sure about what it changes in terms of our response, aside from the imperative to keep immunocompromised patients well isolated from each other.

 

[Doodler]

Not sure what you mean by "increased" here. Increased from what?
In any case, FIV mutates quite a good bit faster than SARS-CoV-2.

Increased relative to control animals that didn't have FIS. Mutational rates in FIV weren't measured, it was there to provide an immunocompromised environment for a different virus. (Again iirc, I will see if I can find a link.)

 

[elbows]

I'm never happy when companies have possibly been selective with their data in order to sugar coat things.

US agency questions AstraZeneca's Covid vaccine trial data

Drug firm may have provided incomplete view of efficacy data from US trial, says safety monitor

www.theguardian.com

The NIAID statement said the DSMB “was concerned by information released by AstraZeneca on initial data from its Covid-19 vaccine clinical trial. The DSMB expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.”

It urged the company “to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible”.

UK scientists said it was unusual for a data safety monitoring board to intervene in public, although there were often debates with the manufacturers behind the scenes. “This is unprecedented in my opinion,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine.

“One explanation might well be that this trial is currently being conducted when there is a large amount of a new variant about more recently, and, as might be expected, the efficacy against that variant might be less, so more recent data shows reduced efficacy. Of course, the other vaccines may also show such reduced efficacy and we don’t know by how much.”

Evans said he was not particularly concerned, “unless they had found a safety issue that was being hidden, which does not appear to be the case”.

 

[gentlegreen]

Just heard on TWIV Danish medical staff being advised to aspirate when giving AZ (uniquely ?) to avoid veins ?
The unstabilised spike was mentioned again more than once.

 

[gentlegreen]

 

[elbows]

I'm never happy when companies have possibly been selective with their data in order to sugar coat things.

US agency questions AstraZeneca's Covid vaccine trial data

Drug firm may have provided incomplete view of efficacy data from US trial, says safety monitor

www.theguardian.com

A pretty modest adjustment now that they've included latest data:

The Anglo-Swedish firm has now adjusted the efficacy rate of its vaccine from 79% to 76%.

Further data from the US trial showed efficacy among the over 65s rose from 80% to 85%.

Fergus Walsh says:

It is now clear that the numbers have not moved by much and it begs the question why such a row over data was not conducted in private. AstraZeneca has risked reputational damage as a result of the public ticking off and senior figures are privately dismayed by the row.

So why didn't AstraZeneca simply wait? I'm told that the company felt a duty to publish results on Monday as soon as the agreed threshold of cases had been passed. A key reason was that there was a specific analysis showing there were no safety issues regarding blood clots. Given that a few EU countries are still not using the vaccine because of concerns over clots, this information would provide reassurance.

Covid vaccine: AstraZeneca updates US vaccine efficacy results

The vaccine-maker slightly amends its efficacy rates as it awaits US regulatory approval.

www.bbc.co.uk

I'd actually prefer such rows and rebukes to be conducted in public, but I am aware that this has implications in terms of public perceptions etc. All the same, I believe in actual transparency and conducting stuff in the public sphere, not mere lip service to the principal whilst clinging firmly to all the usual justifications for handling stuff behind closed doors.

 

[elbows]

These people seem to have had the right idea about how far behind Italy we were at the start. I'm posting it in this thread because this is just one small detail in a story about the impressive clinical trials the UK got up and running quickly:

Covid: The London bus trip that saved maybe a million lives

A conversation on a bus led to the setting up of the Recovery trial, leading to treatments for Covid.

www.bbc.co.uk

The two bus passengers were Prof Martin Landray, a doctor and designer of large-scale drug trials, and Sir Jeremy Farrar, director of the Wellcome Trust, one of the world's biggest funders of medical research - and one of the funders of Recovery.

The date was 9 March 2020. The pair were discussing the impending pandemic, the scenes coming out of Italy, which was the first country in Europe to feel the devastating impact of the virus, and the inevitability of the UK facing the same.

"What we agreed on that bus trip was that the tsunami would arrive within a couple of weeks and we had to have a trial up and running within two weeks," Prof Landray told Inside Health on BBC Radio 4.

 

[zahir]

More on the Astra Zeneca blood clotting issue (thread).

 

[weltweit]

Should administrators of the AZ vaccine be aspirating on injecting?

 

[LDC]

Should administrators of the AZ vaccine be aspirating on injecting?

Not the advice currently, and there's no evidence to suggest anything needs to change.

 

[gentlegreen]

AstraZeneca vaccine renamed ..."Vaxzevria"

Doubtless planned for a while, but will probably fuel the conspiracies ...

Vaxzevria (previously COVID-19 Vaccine AstraZeneca) | European Medicines Agency

www.ema.europa.eu

Covid-19 : critiqué, AstraZeneca rebaptise son vaccin Vaxzevria
L’Agence européenne du médicament a validé le changement de nom du vaccin du labo anglo-suédois. Le sérum, lui, ne change pas.

Par Le Parisien
Le 30 mars 2021 à 16h36

Covid-19 : critiqué, AstraZeneca rebaptise son vaccin Vaxzevria

L’Agence européenne du médicament a validé le changement de nom du vaccin du labo anglo-suédois. Le sérum, lui, ne change pas.

www.leparisien.fr

 

[elbows]

Because of recent events such as Germany restricting AZ vaccine for the under 60's ( eg Covid: Germany limits use of AstraZeneca Covid jab for under-60s ), the BBC have taken another look at the issues involved.

AstraZeneca: Is there a blood clot risk?

Unusual clots have been detected in a handful of people after being injected with the jab.

www.bbc.co.uk

 

[Bahnhof Strasse]

Good article about why some of us feel shit after the jab and others feel nothing at all: Vaccine side effects: My experience of them and what they mean

 

[gentlegreen]

I hope they figure this out quickly - given the AZ ostensibly delivers the same result - spike proteins at the cell membrane for T cells to target.
The MRNA vaccines at the moment look like being the winner - apart from the storage temperature issues - and rare allergic reactions to the lipid nano-wotsits...

 

[gentlegreen]

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[gentlegreen]

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[Cloo]

Possible treatment that could aid recovery and reduce harm to vulnerable people who catch COVID: Covid: Asthma drug 'speeds up recovery at home'

 

[2hats]

There are some 20-odd studies now indicating that one mRNA vaccine dose in convalescents provoke a strong antibody immunoresponse (can be ten to hundred fold that of seronegatives). Here the first longitudinal T cell study examining responses to (mRNA) doses in convalescents and the infection naive also suggesting that the former only require one dose and, mirroring antibody responses, the T cell response typically appears to be greater. The study also confirms cross-variant T cell reactivity and additionally suggests that convalescents post-vaccination T cells may better home to the respiratory tract.

DOI: 10.1101/2021.05.12.443888.

 

[two sheds]

Possible treatment that could aid recovery and reduce harm to vulnerable people who catch COVID: Covid: Asthma drug 'speeds up recovery at home'

Came out a while ago - strange that the article doesn't mention that it's the brown inhaler. Hopefully other steroid inhalers will help too.

 

[Supine]

Covid/Flu combination vax are being trialled. If it works it’s be a great way to keep on top of both virus’s with one visit to a gp.

 

[2hats]

Results of Novavax phase III UK trial (15,000 adults 18-84 years of age, including 27% over age 65) just beginning to surface. NVX-CoV2373 (two dose protein sub-unit) 100% effective against severe disease, hospitalisation and death. 96.4% effective against original SARS-CoV-2 virus and 86.3% effective against B.1.1.7.

Novavax Confirms High Levels of Efficacy Against Original and Variant COVID-19 Strains in United Kingdom and South Africa Trials | Novavax Inc. - IR Site

ir.novavax.com

Preprint confirming NVX-CoV2373 phase III trial results. 89.7% efficacy with respect to symptomatic infection against a mix of B.1.1.7 and earlier variants after second dose (21 day dosing interval). No hospitalisations or deaths in the vaccine arm. >15k participants, >27% 65+, 48.5% female, 94.5% white, 45% had comorbidities for increased risk from COVID-19. Reactogenicity mild and transient, few serious adverse events.
DOI: 10.1101/2021.05.13.21256639

EUA filing perhaps in July if multi-site manufacturing consistency issues can be ironed out. Manufacturer also looking to set up production in Australia to supply the Asia-Pacific region.

 

[2hats]

TeenCOVE phase 2/3 study in the US of mRNA-1273 in 3,700 participants aged 12-17. No cases of COVID-19 were observed in participants who had received two doses of the Moderna COVID-19 vaccine. In addition, a vaccine efficacy of 93% (to symptomatic infection) in seronegative participants was observed starting 14 days after the first dose (confirmed by PCR).

Moderna Announces TeenCOVE Study of its COVID-19 Vaccine in Adolescents Meets Primary Endpoint and Plans to Submit Data to Regulators in Early June | Moderna, Inc.

Primary endpoint of non-inferior immunogenicity versus the Phase 3 study adult comparator group was met No cases of COVID-19 observed after two doses of vaccine using the primary case definition, consistent with a vaccine efficacy of 100% Safety and tolerability generally consistent with Phase 3

investors.modernatx.com

 

[elbows]

Good stuff, although I suppose for the sake of completeness I have to note they did it at a time where only 4 people in the placebo group ended up getting infected.