Possible vaccines/treatment(s) for Coronavirus

[2hats]

A letter (OHSU) reporting a small study of 'breakthrough' vaccination and hybrid immunity.

26 participants (mean age 38 years, convalescents screened out) who had been vaccinated with two-dose BNT162b2 and experienced infection around 210 days after the second dose. A control cohort of BNT162b2 vaccinees with no history of infection was matched to this for comparative purposes. Convalescent vaccinee samples were taken (on average) ~1 month after infection and ~7 months after vaccination; vaccinee only samples were taken ~1 month after last dose.

The study reproduced the previously seen jump in spike RBD, IgG titres and neutralising breadth to assorted VOC (live virus assay) that has been seen in other hybrid studies. All were significantly higher than in two-dose only vaccinees. In addition they measured IgA titres and found those to be significantly higher too - indeed in the vaccinee only cohort their IgA levels were barely above the lower limit of the assay. This last result highlights how the immune response is modulated by the route of exposure to antigen (and points to, as seen in other studies, how advantageous intranasal/oral vaccines could prove to be).

Unfortunately they omitted comparative cohorts of convalescent vaccinees and a control of unvaccinated naives.
DOI: 10.1001/jama.2021.22898.

 

[gentlegreen]

TWIV considers the cost-benefit of vaccinations in the light of J&J being almost out of the picture in the US due to the clotting issues- with effect on (AZ) vaccine uptake elsewhere ... through the lens of whether to vaccinate children (guest is a paediatrician)- plus scepticism about boosters for younger people - i.e. two doses quite likely sufficient if the aim is as belt and braces against serious disease ...

 

[2hats]

Latest study from LJI (Sette, Crotty, et al) looking into T cell responses and steps towards understanding those as correlates of various levels of protection (to infection, to disease, to severe disease, etc).

They quantified the T cell responses from some ~200 donors with varying infection and vaccination histories - grouped as: no infection nor vaccination (I-V-), infected/not vaccinated (I+V-), vaccinated only (V+I-), and infected then vaccinated (I+V+) aka 'hybrid'. By comparing the relative activity directed against spike with that directed at the rest of the viral proteome based on optimised pools of CD4 and CD8 epitopes they were able to define means of classifying each donor group. Vaccinees received either standard two-dose regimens of mRNA-1273 or BNT162b2. Donor groups' median ages ranged 25-42 years, overall age range 17-74 years.

Next they were able to classify the immunoresponse histories of a fresh group of donors with 85-90% accuracy.

T cell responses of vaccinated then infected 'breakthrough' donors, V+I+, were then assessed using this method. (Notably, all the breakthrough infection episodes were mild).

Whilst many of the V+I+ individuals exhibited similar T cell responses to I+V+ hybrids, outperforming I-V-/I+V-/V+I-, suggesting that both B and T cell responses were increased as a result of post vaccination infection, V+I+ 'breakthroughs' also featured a higher degree of heterogeneity in responses compared to I+V+, with around one-third exhibiting similarly lower CD4 responses of I+V- (unvaccinated convalescents), perhaps indicative of vaccination tending to blunt the adaptive immune response to pathogen exposure (as it successfully moderates the disease).

Separately, this approach may prove to be a useful assay in helping accurately assess longitudinal vaccination studies.
DOI: 10.1101/2021.12.15.472874.

 

[2hats]

(Shanghai) An omicron/B.1.1.529 pseudovirus neutralisation study, involving 292 healthcare workers, for Sinopharm's BBIBP-CorV inactivated virus third-dose booster.

8-9 months after dose two in this homologous series SARS-CoV-2 specific antibody levels were found to have dropped significantly. Though they rose dramatically in the vast majority of participants at one month after a third dose booster and pseudovirus neutralisation of early-type jumped 6-fold (compared to levels one month after second dose), neutralisation activity to omicron dropped over 20-fold.


This study does not of course evaluate other aspects of adaptive immunity, and this type of vaccine may take longer than one month to develop an optimal immunogenic response in vaccinees.
DOI: 10.1101/2021.12.17.21267961.

 

[2hats]

Moderna announce preliminary 50µg and 100µg third-dose booster results for mRNA-1273 vaccines.

The authorised booster (50µg of mRNA-1273) increases omicron/B.1.1.529 neutralising antibody levels approximately 37-fold; a 100µg booster dose of mRNA-1273 increases omicron neutralising antibody levels approximately 83-fold (sampled at one month post-booster; both factors relative to pre-boost levels; pseudovirus assay). Multivalent vaccine candidates mRNA-1273.211 (WT+beta) and mRNA-1273.213 (WT+delta) were also tested at the same dosing levels and achieved similar levels of neutralisation.

Moderna will continue to advance an omicron-specific booster (mRNA-1273.529) to clinical trials early next year.

Moderna Announces Preliminary Booster Data and Updates Strategy to Address Omicron Variant

Authorized booster (50 µg of mRNA-1273) increases Omicron neutralizing antibody levels approximately 37-fold; a 100 µg booster dose of mRNA-1273 increases Omicron neutralizing antibody levels approximately 83-fold M oderna will continue to advance an Omicron-specific booster ( mRNA-1273.529) to...

investors.modernatx.com

A preprint is in work.

 

[elbows]

Sotrovimab in the UK news:

Covid: Vulnerable NHS patients to be offered new drug

The drug - sotrovimab - is given as an infusion to high-risk patients who have caught the virus.

www.bbc.co.uk

 

[Dogsauce]

Sotrovimab in the UK news:

Covid: Vulnerable NHS patients to be offered new drug

The drug - sotrovimab - is given as an infusion to high-risk patients who have caught the virus.

www.bbc.co.uk

I had an email from the NHS today about a treatment they would offer me if testing positive, I guess it must be this.

Spoiler: Longish message from NHS

^20/12/2021

Your NHS number: xxxx

Your reference code: xxxx

Dear xxxx,

Important information about new treatments for coronavirus.​

The NHS is using new treatments for coronavirus. Your medical records show that you might be suitable for these treatments if a PCR test confirms that you have coronavirus.

These treatments need to be given quickly after you start to feel unwell. They can stop you from getting seriously ill. More information: Treatments for coronavirus (COVID-19)

You should:​

Have a PCR test kit ready at home. Take a PCR test if you get coronavirus symptoms. If the PCR test confirms that you have coronavirus: the NHS will call you to tell you how you might get a treatment.

Coronavirus treatments can help you if you are ill, but vaccination is still the best protection for you and your loved ones.

1. Have a PCR test kit ready at home​

NHS Test & Trace are sending you a PCR coronavirus test kit to keep so that you can get tested quickly if you have any coronavirus symptoms.

This kit will be sent to the address that you have provided to the NHS. Tell your GP as soon as possible if your address has changed. NHS Test & Trace can send replacement tests.

Call 119 for advice, selecting the option for Test & Trace, if:

you have not received a PCR test by 10 January 2022 you develop symptoms before your PCR test arrives you lose your PCR test or it has any damage or missing parts.

2. Take a PCR test if you get coronavirus symptoms​

Use your PCR test if you develop any coronavirus symptoms, even if they are mild: a high temperature, a new continuous cough (coughing a lot for more than an hour, or 3 or more coughing episodes in 24 hours), a loss or change to your sense of smell or taste.

If you get coronavirus symptoms and don’t have a PCR test kit at home, you can still get a PCR test by phoning 119 or visiting Get a free PCR test to check if you have coronavirus (COVID-19).

When registering a PCR test, it is very important that you enter your NHS number and postcode correctly. This lets you get your test result and allows the NHS to contact you about treatment if you have coronavirus.

3. If the PCR test confirms that you have coronavirus​

If the PCR test shows that you have got coronavirus, the NHS will contact you within 24 hours to arrange a telephone appointment with a health professional.

If you are not contacted about treatment within 24 hours of your positive PCR test result, please contact your GP surgery or call 111. They can make an urgent referral.

Why have you sent me this letter?​

Health experts have looked at the health conditions which put people more at risk of coronavirus. This has been agreed by UK chief medical officers.

Your medical records show that you have, or previously had, one or more of those health conditions, which means that these new treatments might be suitable for you if a PCR test confirms you have coronavirus.

You can find out how the NHS has used your information to identify and contact you about this treatment at Coronavirus (COVID-19) treatments - transparency notice - NHS Digital.

Yours sincerely

Professor Stephen Powis
National Medical Director
NHS England and NHS Improvement

 

[2hats]

The EMA has just recommended granting a conditional marketing authorisation for Novavax's adjuvanted protein-based recombinant vaccine, NVX-CoV2373, aka Nuvaxovid™. The EC has now granted that.

Separately, the WHO has granted NVX-CoV2373 Emergency Use Listing (EUL).

 

[2hats]

Novavax have released results for neutralisation results from phase 3 studies (2019nCoV-101 and PREVENT-19) of their adjuvanted protein subunit vaccine NVX-CoV2373.

The 5µg two-dose primary two-dose vaccination series was found to neutralise all VOCs early-type and all VOCs (beta, alpha, delta and omicron) at 35 days, with neutralisation further jumping substantially after a 5µg third-dose booster given at 6 months.

They also looked at immunoresponses in adolescents (12-17 years) who were given a 5µg two-dose primary series. They observed 100% seroconversion with high neutralising titres to early-type and all VOC( alpha, beta, delta, delta+, gamma, mu and omicron). Immunoresponses were 2-4 times higher than in adults.

Low reactogenicity reported.

They are on schedule to manufacture an omicron-specific vaccine next month.

Novavax says COVID vaccine triggers immune response to Omicron variant

Novavax Inc's COVID-19 vaccine is effective in generating an immune response against the Omicron variant, according to early data published on Wednesday,suggesting that the U.S. drugmaker's existing COVID-19 vaccine can help combat the new Omicron variant.

www.reuters.com

 

[2hats]

An extension of Sigal's recent work - a small study of 13 individuals which would appear to indicate that whilst persons infected by delta/B.1.617.2 are still susceptible to infection by omicron/B.1.1.529, a live virus neutralisation study of sera from vaccinees (either two-dose BNT162b2 or two-dose, ie boosted, Ad26.CoV2.S) infected by omicron (note: minus S:R346K) demonstrated noticeable degrees of neutralisation of delta.

These results are consistent with Omicron displacing the Delta variant, since it can elicit immunity [note: in vaccinees] which neutralizes Delta making re-infection with Delta less likely. In contrast, Omicron escapes neutralizing immunity elicited by Delta and therefore may re-infect Delta infected individuals. The implications of such displacement would depend on whether Omicron is indeed less pathogenic than Delta.

Caution: likely many of the participants in this study (South Africa) have been exposed to beta/B.1.351 some months previous. So it's not yet clear if exposure to omicron after vaccination confers cross-reactivity to delta, or it is activation of cross-reactivity due to some suitably spaced combination of two or all of prior beta/vaccine/omicron exposures. Likely multiple exposures, at sufficient intervals, to more diverse antigens (at least one of which is a dose of a vaccine) drive the neutralisation breadth to VOCs (as seen in hybrid studies).

Implications for the utility of omicron-spike based vaccines in providing greater breadth of cross-protection to other VOC.
DOI: 10.1101/2021.12.27.21268439.

 

[elbows]

 

[existentialist]

That's encouraging, except for the complacency it will undoubtedly foster in our political masters

 

[l'Otters]

There seems to be mixed reception to this
Tweet about Corbevax

Can’t pretend to understand the ramifications of any of the details right now but looks interesting & not found mention of it on this thread.

 

[8ball]

There seems to be mixed reception to this
Tweet about Corbevax

Load of hype and bollox. Doesn't even pick up cat hairs.

Get yersen a Henry.

 

[2hats]

There seems to be mixed reception to this
Tweet about Corbevax

Can’t pretend to understand the ramifications of any of the details right now but looks interesting & not found mention of it on this thread.

For some potential issues see post #10468 in the worldwide thread.

 

[Supine]

There seems to be mixed reception to this
Tweet about Corbevax

Can’t pretend to understand the ramifications of any of the details right now but looks interesting & not found mention of it on this thread.

Not one I’ve followed but AZ is produced license free so cost/profit hasn’t been a factor in its use.

 

[ska invita]

Has anyone heard about Amantadine?
This has become particularly popular in Poland, following a recommendation to use it by a Polish doctor. in Poland people are buying it privately to treat Covid.
I've tried to find debunking articles but can't find anything other than articles stating clinal trials were under way last February (2020), but no results published.

Evaluating Amantadine as a Potential Treatment for COVID-19

Amantadine, a treatment that was originally used as an agent against influenza A, lost efficacy due to viral resistance.

www.pharmacytimes.com

Sales of unproven Covid treatment soar in Poland’s least-vaccinated region

Amantadine, an unproven treatment for COVID-19, has been promoted by some doctors and a deputy government minister.

notesfrompoland.com

 

[LDC]

Has anyone heard about Amantadine?
This has become particularly popular in Poland, following a recommendation to use it by a Polish doctor. in Poland people are buying it privately to treat Covid.
I've tried to find debunking articles but can't find anything other than articles stating clinal trials were under way last February (2020), but no results published.

Evaluating Amantadine as a Potential Treatment for COVID-19

Amantadine, a treatment that was originally used as an agent against influenza A, lost efficacy due to viral resistance.

www.pharmacytimes.com

Sales of unproven Covid treatment soar in Poland’s least-vaccinated region

Amantadine, an unproven treatment for COVID-19, has been promoted by some doctors and a deputy government minister.

notesfrompoland.com

You'd be bonkers to try anything that has not been given approval officially tbh. (E2A: I guess I mean 'one' not 'you' as wasn't aimed at you Ska.)

And when a piece uses sentences like this I'd dismiss the article completely.

"Dr. Wlodzimierz Bodnar, a pediatrician and pulmonologist, became sick with the virus and self-treated with amantadine. His symptoms began to subside within 48 hours of taking the medication."

 

[ska invita]

You'd be bonkers to try anything that has not been given approval officially tbh. (E2A: I guess I mean 'one' not 'you' as wasn't aimed at you Ska.)

And when a piece uses sentences like this I'd dismiss the article completely.

"Dr. Wlodzimierz Bodnar, a pediatrician and pulmonologist, became sick with the virus and self-treated with amantadine. His symptoms began to subside within 48 hours of taking the medication."

theres lots of other more clinical search results and its a pre-existing drug that is available
of course im very sceptical - but its strange not to be able to find a result of the clinical trials mentioned, but I guess it takes longer? or Im not finding them.

 

[elbows]

Has anyone heard about Amantadine?
This has become particularly popular in Poland, following a recommendation to use it by a Polish doctor. in Poland people are buying it privately to treat Covid.
I've tried to find debunking articles but can't find anything other than articles stating clinal trials were under way last February (2020), but no results published.

Its a typical rehash of an old idea. If there is any real merit there, only proper trials can demonstrate it.

When I first got deep into learning about pandemics, it was when fears about H5N1 bird flu first emerged. And Amantadine was one of the existing drugs that some sought solace in, that doomers were tempted to stock up on with the idea they could use it to shield themselves from the worst effects of that flu should it go pandemic in humans.

I wouldnt recommend messing around with it, both because of the lack of evidence and also because of its effects on parts of our bodies which are probably hinted at via what it is currently used for in the world of medicine - parkinsonism. I dont believe in fucking around with the balance of those systems unless there is proven, specific benefit for a particular patient.

 

[LDC]

theres lots of other more clinical search results and its a pre-existing drug that is available
of course im very sceptical - but its strange not to be able to find a result of the clinical trials mentioned, but I guess it takes longer? or Im not finding them.

Just had a quick look, there is some stuff out there.

ClinicalTrials.gov

clinicaltrials.gov

Amantadine Treatment for People with COVID-19

SARS-Cov-2, whose symptoms include difficulty swallowing, coughing, diarrhea, and breathing failure, has caused the loss of many lives around the world. In the absence of a vaccine or medication to help prevent or decrease the effects of the disease, ...

www.ncbi.nlm.nih.gov

Wary though, this one is 15 patients in Mexico, observational and 'with symptoms of covid' ffs; Observational study of people infected with SARS-Cov-2, treated with amantadine - PubMed

 

[gentlegreen]

Once again, amazing that antivaxxers reject a very simple and elegant to all intents "natural" solution but jump on an actual "chemical" shotgun approach ...

I note that it is not recommended for those with prostate or cataract issues ...

 

[Dogsauce]

You'd be bonkers to try anything that has not been given approval officially tbh. (E2A: I guess I mean 'one' not 'you' as wasn't aimed at you Ska.)

And when a piece uses sentences like this I'd dismiss the article completely.

"Dr. Wlodzimierz Bodnar, a pediatrician and pulmonologist, became sick with the virus and self-treated with amantadine. His symptoms began to subside within 48 hours of taking the medication."

That ‘48 hours’ quote has been used more or less verbatim to plug the drug of choice of right wing grifters, Ivermectin, so that triggers my spider senses a bit.

Without suitably sized trials it’s just anecdata and most likely normal recovery in someone with a mild case.

 

[wemakeyousoundb]

That ‘48 hours’ quote has been used more or less verbatim to plug the drug of choice of right wing grifters, Ivermectin, so that triggers my spider senses a bit.

Without suitably sized trials it’s just anecdata and most likely normal recovery in someone with a mild case.

I suspect doing absolutely nothing would have an even better survival rate in my anecdotal trials
report to follow

 

[ska invita]

Cannabis could treat and prevent emerging Covid-19 variants

According to the data, the acids found in cannabis are effective against the alpha and beta variants of Covid-19.

metro.co.uk

 

[2hats]

(UniGe) A preprint of a study providing early indications of vaccine modulation of infectious viral load (as oppose to RNA copies as measured by PCR), such as could influence secondary attack rates.

We assessed nasopharyngeal swabs of COVID-19 patients for quantitative infectious viral titres (IVT) by focus-forming assay and compared to overall virus isolation success and RNA genome copies. We assessed infectious viral titres during the first 5 symptomatic days in a total of 384 patients: unvaccinated individuals infected with pre-VOC SARS-CoV-2 (n=118) or Delta (n=127) and [mRNA] vaccine breakthrough infections with Delta (n=121) or Omicron (n=18).

They observed:

• Low correlation between genome copies and infectious viral titres.
• No correlation between infectious viral load, age and sex of patients.
• Delta/B.1.617.2 infected unvaccinated patients have higher infectious viral load.
• Vaccinated patients have lower infectious viral load than unvaccinated patients.
• In previously vaccinated subjects infection with omicron/B.1.1.529 results in similar infectious viral loads like delta.

In vaccinated vs. unvaccinated Delta infected individuals, RNA genome copies were comparable but vaccinated individuals have significantly lower IVTs, and cleared virus faster. Vaccinated individuals with Omicron infection had comparable IVTs to Delta breakthrough infections.

Note that this study focussed on individuals with high viral loads (ct<27, as measured by PCR) and only in the 5 days following onset of symptoms. The study did not investigate asymptomatic cases.
DOI: 10.1101/2022.01.10.22269010.

 

[2hats]

Not SARS-CoV-2 specific but of great relevance to all vaccine development.

From LJI (Crotty's lab) an investigation (animal study) of germinal centre responses ("evolution in miniature"), the driver of B cell affinity maturation).

In an animal model they immunised with an adjuvanted (saponin-based nanoparticle*) HIV protein vax, using a 'long prime' gradually escalating dosing regimen (slow delivery over 12 days), and an eventual boost dose at 30 weeks, with a view to understanding how long germinal centres might last (designated group 3). They also used a traditional 2-dose approach (group 1, alum adjuvant) and an escalating prime with boost (group 2), both at 10 week dosing intervals.

Germinal centres were observed to persist for over 6 months, without renewed exposure to antigen, indeed up to 9 months.

Following an eventual boost ("second") dose, they observed the highest and broadest HIV neutralising antibody titres seen in this and any previous work.

We have shown that germinal centers (GCs) can persist for greater than six months in response to a priming immunization, with a number of notable outcomes. These findings indicate that patience can have great value for allowing antibody diversification and evolution in GCs over surprisingly extended periods of time. A long prime, adjuvanted, escalating dose immunization approach holds promise for difficult vaccine targets.

DOI: 10.1101/2021.12.20.473537.
*SMNP, a new adjuvant described in detail here - DOI: 10.1126/sciimmunol.abf1152.

 

[2hats]

The EMA has just recommended granting a conditional marketing authorisation for Novavax's adjuvanted protein-based recombinant vaccine, NVX-CoV2373, aka Nuvaxovid™. The EC has now granted that.

Separately, the WHO has granted NVX-CoV2373 Emergency Use Listing (EUL).

Novavax NVX-CoV2373 ('Nuvaxovid') will be offered to people in Belgium from the start of March. Priority will be given to persons allergic to the other vaccine formulations or who experienced adverse side effects after a first dose of one of them.

Belgium will offer Novavax vaccine to those allergic to Pfizer or Moderna

Belgium will start offering the Novavax vaccine to people who are allergic reactions to Pfizer or Moderna or had proven side effects after a first dose.

www.brusselstimes.com

Separately, NVX-CoV2373 has been approved by South Korea's Ministry of Food and Drug Safety.

 

[2hats]

Fresh phase 1/2 trial results for Valneva's whole virus, inactivated, adjuvanted vaccine VLA2001.

Preliminary data (n=30) indicate that a 3-dose series of VLA2001 (two doses a month apart followed by a third booster dose 6-7 months later) demonstrated neutralisation of delta/B.1.617.2 (100% of samples) and omicron/B.1.1.529 (87% of samples). Fold reduction relative to ancestral virus was 2.7-fold for delta and 16.7-fold for omicron. No analysis of T cell activity provided.

Valneva says early studies show COVID-19 vaccine effective against Omicron

French biotech firm Valneva said on Wednesday that preliminary studies showed that three doses of its inactivated COVID-19 vaccine candidate neutralised the Omicron variant of the disease.

www.reuters.com

Valneva are expecting MHRA to be in a position to be able to grant regulatory approval before the end of this quarter.

 

[gentlegreen]

How would they achieve that ?