Possible vaccines/treatment(s) for Coronavirus

[2hats]

Low dose (25µg instead of the current 100µg) mRNA-1273 produces spike antibodies comparable to convalescents; equivalent levels of CD4+ and CD8+ T cells at 6 months post-vaccination.

Subjects with pre-existing crossreactive CD4+ T cell memory had increased CD4+ T cell and antibody responses to the vaccine.

Potential implications for T cell response time and thus reduction in disease severity. Lower dosage could multiply stocks.
DOI: 10.1101/2021.06.30.21259787.

 

[2hats]

Ongoing work on Imperial's saRNA vaccine LNP-nCoVsaRNA (prefusion stabilised spike). Here a phase I trial involving a range of very low 0.1-10µg doses (cf. 100µg and 30µg for mRNA-1273 and BNT162b2, respectively). These were administered as two doses 4 weeks apart. Very well tolerated with clear dosage dependent reactogenticity. Immunogenicity response may point to the need to increasing the dosing interval and refinement to minimise innate recognition of saRNA. A trial with an updated candidate is already underway, looking to enhance RNA expression at very low dose level.

Self-amplifying RNA COVID-19 vaccine technology safe in humans, suggests study | Imperial News | Imperial College London

Results from the first trial of a new COVID-19 vaccine technology show no short-term safety concerns.

www.imperial.ac.uk

 

[2hats]

As per Com-COV (see previous post) another preprint to file under hybrid immunity. A study from Germany, arising from the switch to mRNA vaccines in the wake of elevated risk of AZD1222 linked VITT, heterologous prime-boost vaccination with AZD1222 prime followed by BNT162b2 mRNA boost (9-12 weeks later). A striking increase of vaccine-induced SARS-CoV-2 neutralising antibody activity was observed with significantly higher neutralising antibody titres than either homologous AZD1222 or homologous BNT162b2 vaccination.

DOI: 10.1101/2021.07.03.21258887.

 

[2hats]

A press release regarding a study of efficacy of Johnson & Johnson/Janssen Ad26.COV2.S single dose viral vector to VOCs in South Africa. Efficacy to moderate to serve disease due to beta/B.1.351 is around 64%. New data suggest this vaccine neutralises both beta/B.1.351 and (to a greater degree) delta/B.1.617.2 and gamma/P.1, particularly improving over 8 months. It is not yet clear on what timescale a booster, if any, might be warranted.

Preprint pending.

Preprint - DOI: 10.1101/2021.07.01.450707.

 

[2hats]

Pfizer looking for US regulatory approval for a booster (third) dose of BNT162b2 (particularly in the elderly), sparked in part by evidence of waning antibodies after six months, but also the growth of delta. Though they are redesigning the vaccine to specifically target delta, they think that the current version will provide sufficient protection to it at this time.

Pfizer, BioNTech to seek authorization for COVID booster shot as Delta variant spreads

Pfizer (PFE.N) and partner BioNTech (22UAy.DE) plan to ask U.S. and European regulators within weeks to authorize a booster dose of its COVID-19 vaccine, based on evidence of greater risk of infection six months after inoculation and the spread of the highly contagious Delta variant.

www.reuters.com

 

[2hats]

From Qatar, a matched test-negative, case-controlled study of working age adults vaccinated with mRNA-1273 (standard posology), perhaps appearing to offer better protection to beta/B.1.351. (Note - a predominately young demographic and doubtless a number of confounders).

Effectiveness against B.1.1.7 infection was 88.1% [95%CI: 83.7-91.5%] two weeks or more after the first dose.This rose to 100% [95%CI: 91.8-100.0%] from two weeks after the second dose. For B.1.351 infection this was 61.3% [95%CI: 56.5-65.5%] after the first dose, and 96.4% [95%CI: 91.9-98.7%] after the second. Effectiveness against any severe, critical or fatal COVID-19 disease was 81.6% [95%CI: 71.0-88.8%] after the first dose, rising to 95.7% [95%CI: 73.4-99.9%] after the second dose.
DOI: 10.1038/s41591-021-01446-y.

 

[elbows]

Covid vaccines do work well in clinically vulnerable

A study of more than a million people shows those with other conditions get high protection from two doses.

www.bbc.co.uk

 

[Elpenor]

Heart inflammation link to Pfizer and Moderna jabs

But European regulators say the benefits of Covid vaccines continue to far outweigh the risks.

www.bbc.co.uk

Not sure if I should have second jab tomorrow now. My heart is dodgy and I occasionally get chest pains and breathlessness

 

[prunus]

Heart inflammation link to Pfizer and Moderna jabs

But European regulators say the benefits of Covid vaccines continue to far outweigh the risks.

www.bbc.co.uk

Not sure if I should have second jab tomorrow now. My heart is dodgy and I occasionally get chest pains and breathlessness

The risk is absolutely tiny. The risk to your heart from getting covid badly is many times greater. Go get jabbed

I am in the same position - dodgy heart etc. Not a second thought, the relative risk assessment is overwhelming.

 

[platinumsage]

Heart inflammation link to Pfizer and Moderna jabs

But European regulators say the benefits of Covid vaccines continue to far outweigh the risks.

www.bbc.co.uk

Not sure if I should have second jab tomorrow now. My heart is dodgy and I occasionally get chest pains and breathlessness

Last time I looked the risk was almost exclusively in the under-25s. Tens of millions of doses given to people over that age, millions of whom will have had dodgy hearts (it’s 10% of the Uk population according to BHF), yet basically no cases amongst them.

 

[2hats]

Highlighting strength of hybrid immunity to all variants, necessity of two doses for immunonaives, and perhaps waning of convalescent immunity after many months, two new studies.

A brief study (Emory) of convalescent (31-91 days post infection) and vaccine mediated (mRNA-1273 at 35-51 days, BNT162b2 at 7-27 days, each post second dose) sera neutralisation in live virus assays. Relative to earlier type (WA1/2020) kappa/B.1.617.1 was around 7x less susceptible, whilst delta/B.1.617.2 was around 3x less susceptible, to neutralisation by serum both from convalescents and vaccinees. Despite this finding, a majority of the convalescent sera (79% against kappa and 96% against delta) and vaccine mediated sera had detectable neutralising activity against both variants three months post-infection/second dose. Note the apparent greater degree of immune evasion exhibited by kappa over delta.

DOI: 10.1056/NEJMc2107799.

Second - an extension of an earlier study from France (Institut Pasteur). Here examining neutralisation of sera from convalescents, BNT162b2 and AZD1222 partial/full vaccinees and single dose convalescents (hybrid immunity).

In sera from convalescents at 6 months post-infection (Orléans cohort*) a 4-6x reduction in neutralisation titres (antibodies to spike) against delta/B.1.617.2 was observed (versus alpha and D614G); likewise for another group where sera was collected at 12 months (Strasbourg cohort*). Single dose recipient convalescents (mixture of mRNA-1273, BNT162b2, AZD1222; separate Strasbourg cohort) exhibited strong immunoresponses, which at 12 months post-infection (7-81 days post dose) exhibited a smaller reduction in neutralisation titres against all variants tested, particularly delta/B.1.617.2 and beta/B.1.351.

Classifying neutralisers and non-neutralisers, convalescents varied widely with only around half neutralising beta or delta after one year. All single dose convalescents neutralised all variants at one year. For recipients of Pfizer, with low levels of neutralisation seen after one dose, reduction in neutralising titres after two doses was around 3x for delta and 16x for beta (compared to alpha/B.1.1.7). For AstraZeneca recipients this was 5x and 9x for delta and beta, respectively. Single vaccines doses were poor at neutralising variants. Might hint BNT162b2 recipients would benefit from a later third dose.
* significantly longer post-infection than for the first study (3 months versus 6, 12 months).

DOI: 10.1038/s41586-021-03777-9.

 

[2hats]

The first interim analysis from the phase 1 trial (44k participants) of the Cuban conjugate protein subunit SOBERANA02 vaccine (2 doses, 28 days apart) with SOBERANA-Plus (protein subunit) as a third dose booster (28 days after the second dose). Dominant variant was beta/B.1.351.

Efficacy to infection of the 3 dose course was estimated at 75.7% [95%CI:60.7-85.0]. Efficacy to symptomatic disease was 91.2% [95%CI:77.9-96.5]. Efficacy to severe disease/death was 100%.

Final analysis for the SOBERANA02 (only) 2 dose course efficacy to symptomatic disease was 65.6% [95%CI:52.6-75.0].

 

[2hats]

Results of the Chinese (Sinovac) CoronaVac phase 3 double-blind, randomised, placebo-controlled trial in Turkey (10k participants, aged 18-59, median age 45). CoronaVac is a whole virus inactivated vaccine (with an aluminium hydroxide adjuvant) administered in two doses, 14 days apart.

Efficacy to symptomatic COVID-19, 14 days after dose two, was 83.5% [95%CI: 65.4-92.1] with no deaths seen. The vaccine was well tolerated with a very low number of adverse events. During the early period of this trial the dominant variant was B.1.177 with some early type. In the latter stages alpha/B.1.1.7 came to dominate before giving way to beta/B.1.351.

DOI: 10.1016/S0140-6736(21)01429-X.

 

[Badgers]

Heart inflammation link to Pfizer and Moderna jabs

But European regulators say the benefits of Covid vaccines continue to far outweigh the risks.

www.bbc.co.uk

Not sure if I should have second jab tomorrow now. My heart is dodgy and I occasionally get chest pains and breathlessness

Tiny risk but call your GP to be sure.

With a dodgy heart the vaccine risk is far far lower than Covid

 

[2hats]

Valneva have registered a new phase 3 trial study starting this month, initial reporting by the end of the year. Investigating VLA2001 and VLA2101 (both whole virus inactivated adjuvanted vaccine candidates) in recruits aged 12 and older. No apparent official statement as to what the difference between VLA2001 and VLA2101 is (quite possibly seeded with different variants or even a mix, since dosing was established in phase 1/2 trials).

 

[IC3D]

Not withstanding there is a potential for death still but this is why there isn't a vaccine for the common cold.

 

[cupid_stunt]

Not withstanding there is a potential for death still but this is why there isn't a vaccine for the common cold.

The problem with 'the common cold' as such, is it's not a single virus, it is caused by hundred of variants from several different 'virus families', rhinoviruses, coronaviruses, adenoviruses and enteroviruses being the most common.

 

[elbows]

Thats certainly a big part of the reason things like the cold research unit didnt really get anywhere and got closed down a long time ago.

In terms of things like heart inflammation from Pfizer and Moderna, this phenomenon is perhaps mirroring the same inflammation seen after viral infection that is already known to happen in some young people, same sort of risk profile, ie affects young men.

The risk picture with some common cold viruses is complicated when zooming in, and hasnt received that much attention due to the numbers involved. For example its not hard to find studies that suggest that if you are old and are unlucky enough to require hospitalisation due to rhinovirus, the outcomes are worse than if you are old and hospitalised for influenza. Or that young babies are more at risk of death from RSV than influenza. But note these risks are in relation to the subset of people who are ill enough to be hospitalised with such things, not the wider overall risks relative to the entire pool of infected people. More work is probably required on studying such things, but because the overall numbers are on the low side there has been a lack of impetus.

The minimum we should be doing on this front is to test, test and test again for as many of these viruses as possible so that we get a better picture of reality and tune treatments towards the actual cause.

 

[2hats]

From the Israeli Ministry of Health, information which appear to be part of the as yet unreleased data that are motivating Pfizer to seek authorisation from the FDA and EMA for a third booster.

This appears to suggest BNT162b2 vaccination breakthroughs (in 60+) are strongly correlated with earlier vaccinees (this signal continuing to strengthen). This may be indicative of waning protection from infection after about six months (and particularly in the face of new VOCs). Note (i) protection from serious illness and death maintained, (ii) this cohort includes a large number of the elderly and vulnerable who were vaccinated first, (iii) this is not entirely surprising as initial vaccination induced circulating antibodies would be expected to wane over time and particularly so in those experiencing immunosenescence and/or poor seroconversion.

××××¡× ×× ×©××× ×ק×ר×× × ×× ×××¨× ××× ××× ×©×ת××¡× × ×¨×ש×× ××

××©×¨× ××ר×××ת ×××ק ××× ×שפעת ×××ס×× ×× ×ת×××× ×××××ש ×××¨× ×××¦× ×©× × â¢ × ×ª×× ×× ×©××צ×× ×××××¨× ×××©×¨× ×צ×××¢×× ×¢× ×ת×× ×××ר ××× ×ת××¡× ×× ××ק×××× ××××ק×ת ×××ר××× × ×××ª× â¢ ×××××× ××ת××× ××ק×רת × ×ק×ת: ××× ×× ×ª×× ×× ×× ××××× ×××

www.yediot.co.il

The Israeli Health Minister has already acted on this, likely due to recent growth of delta, and has directed that adults with impaired immune systems, who had received two doses of the Pfizer vaccine, will be offered a booster shot immediately.

Israel offers third shot of Pfizer COVID-19 vaccine to adults at risk

Israel said on Sunday it will begin offering a third dose of Pfizer Inc's (PFE.N) vaccine to adults with weak immune systems but it was still weighing whether to make the booster available to the general public.

www.reuters.com

e2a: Israel have also decided to now provide Pfizer to children under the age of 12 who have underlying health issues.

Health Ministry experts vote to vaccinate under-12s in exceptional cases

Decision coincides with Pfizer clinical trials on safety and efficacy of vaccine among children aged six months to 12 years, will be administered to those considered high risk; team for handling epidemics also okays third shot for residents of nursing homes as national infection rate hits 0.9%

www.ynetnews.com

 

[2hats]

The FDA have advised that Johnson & Johnson/Janssen Ad26.COV2.S may be associated with an elevated risk of developing Guillain-Barré syndrome around two weeks (up to six weeks) after the single dose vaccination. This is observed predominately in older males. Note that the EMA recently advised a slightly elevated risk of developing Guillain-Barré syndrome in recipients of AstraZeneca AZD1222. This may point to a class effect in these viral vector vaccines.

 

[Aladdin]

The FDA have advised that Johnson & Johnson/Janssen Ad26.COV2.S may be associated with an elevated risk of developing Guillain-Barré syndrome around two weeks (up to six weeks) after the single dose vaccination. This is observed predominately in older males. Note that the EMA recently advised a slightly elevated risk of developing Guillain-Barré syndrome in recipients of AstraZeneca AZD1222. This may point to a class effect in these viral vector vaccines.

Is there anything on people who had Guillaine Barre in the past having reactivated disease after vaccination with AZ?

 

[2hats]

The EMA are just monitoring for post-vaccination GBS right now and want healthcare professionals to be alert to the possibility and ensure reporting.

 

[2hats]

A press release regarding a study of efficacy of Johnson & Johnson/Janssen Ad26.COV2.S single dose viral vector to VOCs in South Africa.

Details now published in the NEJM - DOI: 10.1056/NEJMc2108829.

 

[2hats]

Yet more promising heterologous results.

From Germany, a small study of AZD1222 (ChAd) only and AZD1222/BNT162b2 in young (mean age 38) healthcare workers. Significantly higher neutralising antibody responses (to recent VOCs) were seen in the mixed cohort (similar to those seen in the homologous BNT162b2 cohort), with strong spike directed T cells in both cohorts.

DOI: 10.1038/s41591-021-01449-9.

From Sweden, a small study of homologous AZD1222 (mean age 46) and mixed AZD1222/mRNA-1273 (mean age 40) responses in healthcare workers. Higher neutralising titres for the heterologous approach compared to AZD1222 only. Heterologous sera were able to neutralise beta/B.1.351, unlike those from a course of AZD1222.

DOI: 10.1056/NEJMc2110716.

 

[platinumsage]

Nice to see that the WHO are on the ball as usual:

"It’s a little bit of a dangerous trend here. We are in a data-free, evidence-free zone as far as mix and match"

Mixing COVID-19 vaccines a ‘dangerous trend,’ WHO chief scientist says - National | Globalnews.ca

Canada has been mixing COVID-19 vaccine doses since June, after the National Advisory Committee on Immunization approved the idea.

globalnews.ca

 

[Supine]

Nice to see that the WHO are on the ball as usual:

"It’s a little bit of a dangerous trend here. We are in a data-free, evidence-free zone as far as mix and match"

Mixing COVID-19 vaccines a ‘dangerous trend,’ WHO chief scientist says - National | Globalnews.ca

Canada has been mixing COVID-19 vaccine doses since June, after the National Advisory Committee on Immunization approved the idea.

globalnews.ca

They said it wasn’t good for individuals to make up their own rules about mixing and matching. That seems like good advice until formal trials have been completed.

 

[platinumsage]

They said it wasn’t good for individuals to make up their own rules about mixing and matching. That seems like good advice until formal trials have been completed.

WHO's chief scientist said it's a "dangerous trend " and "we are in a data-free, evidence-free zone" which is blatant scaremongering. What are all those people in countries where the health authorities are mixing and matching supposed to think about that? This is why she had to issue a clarification saying people should follow advice. Sure formal trials haven't been completed, but you could say the same about lots of aspects of the vaccination rollout, and that's not the same as there being no suitable data available on which to base decisions.

 

[Riklet]

I hope my double-AZ'd parents get a Pfizer booster this autumn, based on that...

 

[2hats]

Both studies underline why designers of next generation vaccines should consider a border range of virus proteins (eg RTC, nucleocapsid) and not just focus on spike.

From the US (Fred Hutch), a longitudinal study of the immune response to SARS-CoV-2 infection in 254 patients that could further this idea.

Broad, durable immunity was seen for at least 8 months after infection (climbing to a plateau), featuring binding and neutralising antibodies with half-lives in excess of 200 days. Memory B cells, producing IgG antibodies to spike, proliferated and persisted, as did polyfunctional CD4+ and CD8+ T cells. The former equally targeting various SARS-CoV-2 epitopes, the latter preferentially targeting nucleocapsid proteins - perhaps highlighting the importance of considering those antigens when designing future vaccines, particularly in the face of new variants.

Additionally, it was noted that age and disease severity separately, independently drove higher adaptive immune responses (specifically in CD4+ T cell and humoral immunity to SARS-CoV-2), but there was little variation in this with gender.
DOI: 10.1016/j.xcrm.2021.100354.

 

[2hats]

From UCL, an investigation into waning antibody levels to the spike protein, S, in 605 fully vaccinated participants (53% female, 18-90+ years, median age 63, 19% extremely clinically vulnerable, 31% clinically vulnerable; 33% received BNT162b2, 67% AZD1222). Participants provided samples 14-154 days after their second dose.

As noted previously, those with previous infection typically had much higher S-antibody levels than vaccinated non-convalescents. The data suggested waning of S-antibody levels in infection-naive individuals over a 3-10 week period after a second dose of either BNT162b2 or AZD1222, not dissimilar to waning antibodies seen in convalescents shortly after infection, although memory B cell populations are maintained. This behaviour was preserved over age, sex and clinical vulnerability.

DOI: 10.1016/S0140-6736(21)01642-1.