Possible vaccines/treatment(s) for Coronavirus

[2hats]

Another single dose mRNA vaccine for seropositives study, here from the Netherlands. This one widens the knowledge base, using BNT162b2, indicating a strong immune response within a week of one dose, with neutralising antibody titres far exceeding those of seronegatives (control group measured two weeks after second dose). This was found to be true for a broad range of ages (22-88 years), for a range of previous COVID infections (mild-moderate-severe-critical), was largely unaffected by comorbidities, and little affected by time since infection (from 1 to 15 months). As in other vaccine studies, younger participants, female participants, had a tendency towards slightly higher neutralisation responses.

DOI: 10.1101/2021.05.25.21257797.

 

[2hats]

And again! Here a study of humoral and cellular immune responses after each dose (of BNT162b2) for seropositives, compared to seronegatives. As before, large antibody and T cell responses after a single dose for convalescents. Also, T cell activation preserved across B.1.1.7 and B.1.351 variants.

DOI: 10.1126/sciimmunol.abj1750.

 

[2hats]

MHRA regulatory approval for the single dose recombinant, replication incompetent, adenovirus vector vaccine Janssen (Johnson & Johnson) Ad26.COV2-S EUA in the UK.

 

[elbows]

Some of the UK attempts to analyise effectiveness of vaccines to prevent symptomatic disease and mortality. Preprints from the month of May.

Effectiveness of BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on mortality following COVID-19

We estimated risk of death in vaccinated compared to unvaccinated COVID-19 cases. Cases vaccinated with 1 dose of BNT162b2 had 44% reduced risk of death, 55% with 1 dose of ChAdOx1, and 69% with 2 doses of BNT162b2. This is on top of the protection provided against becoming a case. ###...

www.medrxiv.org

Effectiveness of COVID-19 vaccines against the B.1.617.2 variant

Background The B.1.617.2 COVID-19 variant has contributed to the surge in cases in India and has now been detected across the globe, including a notable increase in cases in the UK. We estimate the effectiveness of the BNT162b2 and ChAdOx1 COVID-19 vaccines against this variant. Methods A test...

www.medrxiv.org

 

[elbows]

This isnt a treatment but I was lacking ideas about which thread to stick it in.

 

[prunus]

This isnt a treatment but I was lacking ideas about which thread to stick it in.

“It is known that the human leukocyte antigen gene identified, HLA-DRB1*04:01, is directly correlated to latitude and longitude. This means more people in the North and West of Europe are likely to have this gene.

This suggests that populations of European descent will be more likely to remain asymptomatic but still transmit the disease to susceptible populations.”

Interesting given the observed outcomes differential in ethnic groups in the UK; also perhaps severity of outbreak in Italy?

 

[elbows]

“It is known that the human leukocyte antigen gene identified, HLA-DRB1*04:01, is directly correlated to latitude and longitude. This means more people in the North and West of Europe are likely to have this gene.

This suggests that populations of European descent will be more likely to remain asymptomatic but still transmit the disease to susceptible populations.”

Interesting given the observed outcomes differential in ethnic groups in the UK; also perhaps severity of outbreak in Italy?

I havent had much time to think about the details.

And I suppose it gets complicated quickly - eg asymptomatic cases and transmission are really bad news for controlling the size of outbreaks.

There are probably numerous reasons why parts of Italy had a bad wave, very much including the fact their early surveillance was very poor. If you dont really notice that youve got community transmission until you start noticing plenty of deaths 'all of a sudden' (when reality was not actually so sudden, just detection of it was sudden), then thats a sign things are going to get very bad very quickly. And thats certainly what happened with Italy at the start, I remember using their first news of deaths as my main fire alarm at the time. None of that means you are saying anything wrong, just that there are multiple factors.

 

[2hats]

Preclinical testing in animal models of (non-prefusion-stabilised) AZD2816, which features B.1.351 spike, demonstrates strong immunoresponse to a one dose booster (to previous immunisation with AZD1222). Neutralisation titres against B.1.351, B.1.617.1 and B.1.617.2 were observed and no evidence of original antigenic sin was seen. The breadth of post two-dose AZD1222 cellular immune response was preserved (the frequency of antigen specific T cells was maintained). No clear indication of modification to address venous thrombosis issues.

DOI: 10.1101/2021.06.08.447308

 

[2hats]

Pre-clinical testing in animal models of Novavax with B.1.351 spike protein, NVX-CoV2373 (rS-B.1.351). Strong immune response seen whether it was used alone, mixed or as a heterologous prime-boost to earlier vaccination with the original NVX-CoV2373 (rS-WU1), even a year later. It induced both protective antibody and cell-mediated responses that were effective against B.1.1.7 and B.1.351.
DOI: 10.1101/2021.06.08.447631.

 

[2hats]

Novavax have announced the outcome of their US/Mexico ~30k participant, placebo-controlled, observer-blinded, randomized study (during which time B.1.1.7 came to dominate).

NVX-CoV2373 (a protein-based recombinant nanoparticle vaccine with a saponin-based Matrix-M adjuvant) demonstrated overall efficacy of 90.4% (95% CI: 82.9, 94.6) to PCR confirmed symptomatic infection. Seventy-seven cases of COVID-19 infection were observed: 63 in the placebo group (10 moderate, 4 severe) and 14 in the vaccine group (all mild). This indicates a vaccine efficacy of 100% (95% CI: 87.0, 100) against moderate or severe disease. Sequencing of cases indicated 100% efficacy (95% CI: 80.8, 100) against non-VOC/VOI, with vaccine efficacy against VOC/VOI of 93.2% (95% CI: 83.9, 97.1). NVX-CoV2373 also showed success among "high-risk" populations (defined as 65+, and <65 with certain comorbidities, or having life circumstances with frequent COVID-19 exposure): here vaccine efficacy was 91.0% (95% CI: 83.6, 95.0).

Safety data from the trial indicated the vaccine was generally well tolerated.

Novavax intend to seek regulatory approval in the US and Europe by the end of September, by which time they hope to be producing around 100 million doses per month, rising to 150 million per month by the end of the year.

No preprint yet, but a press release is available.

 

[elbows]

 

[Supine]

Amazing Horizon show where they follow five of the vaccine teams through the vaccine development process. So proud of science

BBC Two - Horizon, 2021, Horizon Special: The Vaccine

The extraordinary inside story of the vaccine scientists who took on Covid-19 - and won.

www.bbc.co.uk

 

[William of Walworth]

Amazing Horizon show where they follow five of the vaccine teams through the vaccine development process. So proud of science

BBC Two - Horizon, 2021, Horizon Special: The Vaccine

The extraordinary inside story of the vaccine scientists who took on Covid-19 - and won.

www.bbc.co.uk

The Guardian's Lucy Mangan reviews that programme here -- she was so positive, that it made me want to watch it ASAP!

 

[2hats]

Preprint of a new study (largely out of Oxford), of convalescent and vaccinee sera (collected across the UK) versus recent VOCs, suggests that those sera show reduced neutralisation of B.1.617.1 and B.1.617.2. Additionally sera from B.1.351 and P.1 convalescents exhibit a marked reduction in neutralisation of B.1.617.2. The authors find that the VOCs B.1.351, P.1 and B.1.617.2 are antigenically divergent - convalescent sera from one barely neutralises the other. The authors conclude that vaccines based on B.1.1.7 may broadly protect against current variants. Vaccinees receiving AZD1222 or BNT162b2 were found to still produce good neutralising titres against B.1.617.2 (only modest reductions).

DOI: 10.1016/j.cell.2021.06.020.

Note: Vaccine sera collected 1-4 weeks post second dose. Some of the AZD1222 vaccinees were in the early LD/SD trial arm. Mean age of BNT162b2 vaccinees was 37 years.

 

[2hats]

Worth noting that the CureVac mRNA vaccine candidate phase 2b/3 study results have been announced. A disappointing 47% efficacy to COVID-19 disease of any severity. In particular, efficacy was lower in older participants.

CureVac - Wir revolutionieren die mRNA für das Leben der Menschen.

CureVac ist ein globales biopharmazeutisches Unternehmen mit über 20 Jahren Erfahrung in der Entwicklung der mRNA-Technologie für medizinische Zwecke.

www.curevac.com

 

[2hats]

From France, a longitudinal study of memory B cell response and neutralisation in convalescent recipients of mRNA vaccines (BNT162b2) versus non-convalescent. The convalescents (severe: S-CoV; mild: M-CoV) received one dose (here termed 'boost') typically just under one year after original infection and were compared to naive subjects receiving the standard two dose vaccination regimen.

Yet again the high immunoresponses (IgG antibody levels) of convalescents receiving single-dose was noted, but also the breadth of memory B cell responses two months later. Notably, sera of single-dose recovered patients had neutralisation potency to B.1.351, whilst sera of fully vaccinated naive subjects were significantly less capable in this respect. This and other observations suggest that maturation of B cells after repeated exposure to spike (whether natural infection or mRNA vaccination mediated) likely offers protection against a wide range of variants (which could bolster the case for periodic booster doses, particularly focussed on non-convalescents).

these data describe an immune response maturing with time in SARSCoV-2 convalescent patients, and resulting in a massive, high-affinity response after vaccination, which [...] displays an improved recognition of the RBD variants [ie VOCs] as well. In this immune evolution scheme, the response of naive vaccinees nevertheless lags behind the maturation process that took place during infection. Our observations suggest that repeated challenges, even against the original spike protein, will compensate for these differences by recall of affinity-matured memory B cells and allow vaccinated people to cope efficiently with most variants actually described.

DOI: 10.1101/2021.06.17.448459.

 

[Aladdin]

How long will full Pfizer vaccination protect against the Delta variant? Is there anything out on this and in layman's terms?

 

[elbows]

How long will full Pfizer vaccination protect against the Delta variant? Is there anything out on this and in layman's terms?

They cant tell in advance of it waning. They cannot speed up time when doing such experiments, so this is something that will become evident only when a time comes that real-world surveillance of the situation points in such a direction.

Plus if they just try to figure it out using waning antibody levels then they are missing out other important aspects of the immune response, such as at the cellular level, via t-cells etc.

 

[cupid_stunt]

How long will full Pfizer vaccination protect against the Delta variant? Is there anything out on this and in layman's terms?

Long term is unknown with all current vaccines, because they haven't been around long enough.

In the here & now, IIRC, it offers 96% protection against severe illness & hospitalisation from the Delta variant, 92% for the AZ vaccine.

Yep...

The analysis suggests:

• the Pfizer-BioNTech vaccine is 96% effective against hospitalisation after 2 doses
• the Oxford-AstraZeneca vaccine is 92% effective against hospitalisation after 2 doses

Vaccines highly effective against hospitalisation from Delta variant

New analysis by PHE shows for the first time that 2 doses of COVID-19 vaccines are highly effective against hospitalisation from the Delta (B.1.617.2) variant.

www.gov.uk

 

[elbows]

And if/when the real world data suggests something is happening, they will have to be careful to see if they can determine whether its actually caused by waning immunity as opposed to a new variant that can escape some chunk of prior immunity.

 

[Aladdin]

Long term is unknown with all current vaccines, because they haven't been around long enough.

In the here & now, IIRC, it offers 96% protection against severe illness & hospitalisation from the Delta variant, 92% for the AZ vaccine.

Yep...

Vaccines highly effective against hospitalisation from Delta variant

New analysis by PHE shows for the first time that 2 doses of COVID-19 vaccines are highly effective against hospitalisation from the Delta (B.1.617.2) variant.

www.gov.uk

This may be a stupid question but will vaccination stop you getting the virus ?

 

[Aladdin]

They cant tell in advance of it waning. They cannot speed up time when doing such experiments, so this is something that will become evident only when a time comes that real-world surveillance of the situation points in such a direction.

Plus if they just try to figure it out using waning antibody levels then they are missing out other important aspects of the immune response, such as at the cellular level, via t-cells etc.

So does this really mean that the pandemic is not over even when we are at 85% to 90% population vaccinated?

 

[2hats]

How long will full Pfizer vaccination protect against the Delta variant? Is there anything out on this and in layman's terms?

Unknown and will vary from individual to individual.

This may be a stupid question but will vaccination stop you getting the virus ?

Only via risk reduction at the population level. At the level of virus challenge of an individual, no. To what degree it replicates though will, again, vary from individual to individual.

 

[prunus]

This may be a stupid question but will vaccination stop you getting the virus ?

Yes. At least some of the time, with some not yet precisely quantified.

 

[Aladdin]

Unknown and will vary from individual to individual.

Only via risk reduction at the population level. At the level of virus challenge of an individual, no. To what degree it replicates though will, again, vary from individual to individual.

That is quite worrying.

 

[prunus]

Unknown and will vary from individual to individual.

Only via risk reduction at the population level. At the level of virus challenge of an individual, no. To what degree it replicates though will, again, vary from individual to individual.

I’m not sure that’s quite accurate, or rather it might be too accurate for a normal interpretation of what ‘getting’ the virus means, even if it turns out not to provide sterilising immunity in any cases.

I think it’s fair to categorise the situation where one is exposed to the virus, it replicates a bit in your cells but is shut down hard by your (vaccine derived) immune response to the extent where you have no effects and have an effective zero probability of passing it on (due to negligible load and or shedding) as ‘not getting the virus’ for most purposes.

 

[Aladdin]

Just one more basic question...
So say a fully vaccinated person gets a variant and doesnt get sick....can they pass it on to someone else who has not been fully vaccinated?

 

[Badgers]

This may be a stupid question but will vaccination stop you getting the virus ?

No.

 

[Badgers]

Just one more basic question...
So say a fully vaccinated person gets a variant and doesnt get sick....can they pass it on to someone else who has not been fully vaccinated?

Yes.

 

[Badgers]

At the testing centres this week we have had a lot of (as a %) double vaccinated people with no symptoms (vaccine working for them) testing positive.

Including a family of five with parents both working and three kids in school/college. All positive.