Possible vaccines/treatment(s) for Coronavirus

[2hats]

Very preliminary data from a further neutralisation study (Medizinische Universität, Innsbruck). Details a little lacking right now but apparently live virus neutralisation assays.

(Short) preprint of the study now available. Small study size (7-20 participants in each cohort). Note that delta/B.1.617.2 sera donors were all young (<=30 years) whilst beta/B.1.351 donors where predominately elderly (60-90 years). All other cohorts had a reasonable spread of ages (~20-90years). All the previously infected vaccinees were single dose recipients.
DOI: 10.1101/2021.12.08.21267491.

 

[2hats]

Jerusalem Post reporting an Israeli (Sheba) neutralisation study (of 40 healthcare workers; half double dosed 5-6 months ago and half treble dosed). This found that three shots of BNT162b2 are four times less effective against omicron/B.1.1.529 than against delta/B.1.617.2 (at one month post third dose). However that third dose was found at one month to boost levels around 100-fold over the two-dose regimen at 5-6 months. The Ministry of Health is considering recommending people get a third dose after an interval of 3 months.

e2a: slide from MoH presentation. Live virus assay. 20-fold reduction in neutralisation for original BNT162b2 two-dose regimen versus omicron compared to early wild-type. 9-fold reduction in neutralisation for BNT162b2 three-dose regimen versus omicron compared to early wild-type. No details on timings and cohort demographics.

 

[2hats]

An extensive longitudinal study (UMontreal and others) of the variation of humoral immunoresponse between both convalescent (27 persons infected 4-12 months prior to first dose) and non-convalescent individuals (26) who have been vaccinated (original two-dose regimen) with BNT162b2 at short (~4 week; range 3-5 weeks) and long (~16 week; range 11-19 weeks) intervals. 12 of the convalescents received only one dose of BNT162b2. Age range of participants was 21-65 years.

Neutralisation was measured with a lentivirus based pseudovirus assay and immunoresponse characterised further with an antibody-dependent cellular cytotoxicity assay.

Key points from this study:

• replicated hybrid immunity results seen in several previous studies
• demonstrated second dose for hybrid antibody response was not necessary though it did reduce heterogeneity in immunoresponses on a shorter timescale; first dose achieves high antibody potency and breadth (note: this says nothing about whether a second dose might influence cellular responses)
• hybrids were observed to have strong immunoresponses to previously unencountered VOCs
• hybrid immunoresponse waned less quickly than that of naive vaccinees, remaining relatively stable for at least 8 months
• the long dose interval improved immunoresponse for two-dose naives, but most importantly greatly improved neutralisation to VOCs, compared to the short dose interval - IgG RBD avidity suggested that this longer interval facilitates maturation of B cells in the germinal centre
• notably IgA was significantly higher in convalescents post-vaccination (with implications for infection and transmission reduction)
• the results might suggest that there could be advantage in a suitably long interval to a third (booster) dose for previous naive two-dose short interval vaccinees - improving neutralisation breadth to VOCs
• irrespective of dosing interval, convalescent vaccinees exhibited enhanced degrees of cross-reactivity to other coronaviridae (HKU1, SARS-CoV) that naive vaccines did not

DOI: 10.1016/j.chom.2021.12.004

TL;DR:

Previously infected individuals appear to only need one mRNA vaccine dose to produce strong, robust immunity. A longer dosing interval for the previously uninfected significantly improves their immune response. Antibodies wane sooner in previously uninfected vaccinees compared to convalescents.

This paper is discussed in TWiV 839 (from 30 minutes in).


(UBC) A larger study (186 paramedics, aged 33-45 years) also looked into short (~4 week) and long (~6-7 week) dosing intervals covering both BNT162b2 and mRNA-1273 mirrors the previous results. Sampling was around 2 months post second dose. Assays were standard commercial offerings (Roche, MSD). Attempts were made to screen out convalescents.

A SARS-CoV-2 vaccine dosing interval of 6–7 weeks compared with a standard dosing interval (<4 weeks) resulted in higher anti-spike antibodies detected in the blood of vaccinated individuals.

DOI: 10.1093/cid/ciab938.

 

[elbows]

I think the link to the first paper might be mangled.

 

[2hats]

From Rockefeller, NY, a study of the plasma neutralisation properties of omicron/B.1.1.529 and comparison with their earlier PMS20 polymutant (see post #352, on the mutations thread).

Sera from both convalescents and non-convalescents, some also vaccinees receiving either three-dose mRNA (BNT162b2 or mRNA-1273) or single-dose Ad26.COV2.S (J&J), were evaluated using a HIV-1 based pseudovirus assay.

Whilst sera from convalescents, single-dose J&J and two-dose naive vaccines failed to neutralise both PMS20 and omicron, that from vaccinated convalescents and three-dose naive vaccines (third dose given at >6 months, sera sampled at 1 month after last vaccine dose) both demonstrated substantial neutralisation (as previously, hybrid immunity yields the most strongest immunoresponse). Neutralisation trajectories of vaccinated convalescents and responses of convalescent-only underline the need for previously infected individuals to receive at least one vaccine dose.



Co-PI summary thread.

Early preprint.

 

[2hats]

I think the link to the first paper might be mangled.

Sorry. Now fixed.

 

[Dogsauce]

Presumably this kind of data is what is pushing the drive for people to take the booster? Might the country also not do as badly as some others due to higher levels of ‘hybrid immunity’ due to Delta having been allowed to rip through the population?

 

[2hats]

(MIT/Harvard and others) A (pseudovirus) neutralisation study (239 individuals, ages 18-78, median age of each sub-group 34-46 years, a mixture of healthcare workers and wider community). Here examining the potency of sera from mRNA-1273, BNT162b, and Ad26.COV2.S vaccinees, some of each convalescents, some with and without boosters, some vaccinated recently (<3 months), some in the 'distant' past (6-12 months ago), in respect of various VOC including omicron.

Third dose boosted individuals exhibited the least reduction in neutralisation (compared to early wild-type), namely around 4 to 6-fold. They state:

mRNA vaccine booster induces potent neutralizing responses against SARS-CoV-2 Omicron variant that are low-to-absent in non-boosted vaccinees.

Importantly, note that the omicron pseudovirus here did not feature R346K (eg as seen in the Sigal study).

In particular, they comment:

Although the emergence of variants has catalyzed the development of variant-specific booster shots to increase variant neutralization, our results suggest that current wild type-based mRNA vaccines are sufficient to stimulate cross-reactive humoral responses greater than might have been anticipated. Whether this is the result of booster timing (in most cases >6 months after vaccination) or because the primary series was simply insufficient to fully stimulate B cell responses against each of the possible epitopes on the spike antigen is unclear.

Our results would suggest that these recipients of Ad26.COV2.S vaccines may benefit from additional mRNA vaccine doses with the potential to further raise titers and broaden their neutralizing activity.

Unfortunately this study did not distinguish previously-infected separately as infected-then-vaccinated or vaccinated-then-infected. Notable though is a hint of consistent clustering of results in convalescent vaccinees. Speculation: perhaps suggestive of a dichotomy arising from infected-then-vaccinated versus vaccinated-then-infected ('breakthrough' infection) participants. This would be consistent with similar recent studies (infected-then-vaccinated hybrid immunity easily on a par with immunity induced by a three-dose boosted mRNA course) and Crotty's thoughts.

Besides highlighting the need for non-convalescents to receive a third dose booster, it would hint that vaccinated then infected individuals would also benefit from such an additional dose.
DOI: 10.1101/2021.12.14.21267755.

Author commentary thread.

 

[2hats]

Presumably this kind of data is what is pushing the drive for people to take the booster? Might the country also not do as badly as some others due to higher levels of ‘hybrid immunity’ due to Delta having been allowed to rip through the population?

Any degree of prior immunity will tend to soften outcomes (which is likely what is being seen in South Africa, though twinned with a much younger demographic). However, as per recent studies, infection following two-dose vaccination of the previously seronaive possibly not as effective as either infection prior to vaccination or adequately timed three dose mRNA/heterologous series with mRNA booster.

 

[2hats]

Jerusalem Post reporting an Israeli (Sheba) neutralisation study (of 40 healthcare workers; half double dosed 5-6 months ago and half treble dosed). This found that three shots of BNT162b2 are four times less effective against omicron/B.1.1.529 than against delta/B.1.617.2 (at one month post third dose). However that third dose was found at one month to boost levels around 100-fold over the two-dose regimen at 5-6 months. The Ministry of Health is considering recommending people get a third dose after an interval of 3 months.

e2a: slide from MoH presentation. Live virus assay. 20-fold reduction in neutralisation for original BNT162b2 two-dose regimen versus omicron compared to early wild-type. 9-fold reduction in neutralisation for BNT162b2 three-dose regimen versus omicron compared to early wild-type. No details on timings and cohort demographics.

Preprint of this live virus study is now available.

We analyzed the neutralization efficiency against wild-type, Beta, Delta and Omicron VOC. Limitations of the study include the small cohort tested and this test being only an in-vitro assay. Yet, we demonstrate low neutralization efficiency against delta and wild-type for vaccines with more than 5 months following the second BNT162b2 dose, with no neutralization efficiency against Omicron. We demonstrate the importance of a third dose, by showing a 100-fold increase in neutralization efficiency of Omicron following a third dose, with a 4-fold reduced neutralization compared to that against the Delta VOC. The durability of the effect of the third dose is yet to be determined.

DOI: 10.1101/2021.12.13.21267670.

 

[2hats]

Two more omicron/B.1.1.529 vaccine neutralisation studies.

From Cologne a pseudo virus assay based study of 30 non-convalescent individuals (median age 49, range 27-78 years) vaccinated with the standard two-dose BNT162b2 regimen. Samples were collected at various time points and again after a third dose booster. Additionally 30 convalescents (median age 52, range 22-68 years) were sampled up to a year after infection and again after a single dose of BNT162b2. The advantages of hybrid immunity and three-dose regimens, in neutralising omicron, seen in previous studies were reproduced.

DOI: 10.1101/2021.12.14.21267769.

From Australia (various NSW institutes/hospitals) a small live virus assay study (10 individuals, median age 59 years, range 34-65). One vaccine naive, nine two-dose BNT162b2 and four three-dose BNT162b2 (6 month 2nd-3rd dosing interval). No prior infection for any participants.

Interestingly they made an observation of delays in omicron growth in vitro which might suggest that omicron's "mutational changes may negatively affect viral fitness" and could have implications for incubation period and viral shedding window.

DOI: 10.1101/2021.12.12.472252.

 

[2hats]

From HKU another omicron vaccine neutralisation study. This time sera from BNT162b2 and CoronaVac double-dosed vaccinees (Sinovac's CoronaVac is an inactivated virus vaccine) - 25 individuals of each (median age 48, range 23-61 years). The neutralisation assay was live virus based (performed in a BSL-3), testing against omicron/B.1.1.529 and B.1.1.529+R346K, amongst others.

The study concluded that omicron escapes all neutralisation by standard dosing of CoronaVac and BNT162b2 neutralises it very poorly. The R346K mutation did not appear to significantly affect results.
DOI: 10.1101/2021.12.13.21267668.

 

[2hats]

Phase 3 trial results for Medicago's CoVLP plant-based, virus-like particle, COVID-19 vaccine (two intramuscular doses, 3 weeks apart, storable at standard refrigeration temperatures). 24,000+ participants from six countries, in North America, Latin America, and Europe, aged 18+.

CoVLP is created via a molecular farming technique - by engineering a bacterium with genes of the target virus, then introducing that into a tobacco plant (Nicotiana benthamiana) where the virus-like particles are produced in the leaves, from which they can be harvested, extracted and prepared.

Overall vaccine efficacy for CoVLP against all SARS-CoV-2 variants was 71% (95%CI:58.7-80.0). Amongst confirmed previously-uninfected this was 75.6% (95%CI:64.2-83.7). The vaccine candidate demonstrated efficacy of 75.3% (95%CI:52.8-87.9) against COVID-19 of any severity due to delta/B.1.617.2. Efficacy was 88.6% (95%CI:74.6-95.6) against the gamma/P.1. Omicron/B.1.1.529 was not in circulation at the time of this trial. No related serious adverse events were reported and reactogenicity was generally mild to moderate and transient.

Based on these results, Medicago are seeking regulatory approval for CoVLP from Health Canada.

Medicago and GSK announce positive Phase 3 efficacy and safety results for adjuvanted plant-based COVID-19 vaccine candidate | Medicago

Medicago and GSK announce positive efficacy and safety results from the global Phase 3 study of Medicago’s plant-based COVID-19 vaccine candidate

medicago.com

 

[Riklet]

2hats based on the various studies and data youve posted, what would your take be on booster vaccine timescale for a double jabbed covid convalescent (pre vaccination).

My situation -

Covid in March 2020 and long covid since (much better in past 6 months).
Pfizer vaccine mid June and second end of August.
Booster jab booked for end of December (4 months).

Unsure whether to get the booster in the next few days at a walk in. Or wait til end of month. Or even wait longer. Obviously Omicrom spread is making me consider another jab asap...

 

[prunus]

2hats based on the various studies and data youve posted, what would your take be on booster vaccine timescale for a double jabbed covid convalescent (pre vaccination).

My situation -

Covid in March 2020 and long covid since (much better in past 6 months).
Pfizer vaccine mid June and second end of August.
Booster jab booked for end of December (4 months).

Unsure whether to get the booster in the next few days at a walk in. Or wait til end of month. Or even wait longer. Obviously Omicrom spread is making me consider another jab asap...

I am not 2hats but in case my opinion is of value: get it done now ASAP.

 

[8ball]

I am not 2hats but in case my opinion is of value: get it done now ASAP.

Opinion verified.

 

[platinumsage]

2hats based on the various studies and data youve posted, what would your take be on booster vaccine timescale for a double jabbed covid convalescent (pre vaccination).

My situation -

Covid in March 2020 and long covid since (much better in past 6 months).
Pfizer vaccine mid June and second end of August.
Booster jab booked for end of December (4 months).

Unsure whether to get the booster in the next few days at a walk in. Or wait til end of month. Or even wait longer. Obviously Omicrom spread is making me consider another jab asap...

Put it this way. If you end up in hospital with covid and they ask if you had your booster yet, and you reply that no, you were deliberately delaying it based on what you read on the internet, you’d be met with lots of and

 

[2hats]

2hats based on the various studies and data youve posted, what would your take be on booster vaccine timescale for a double jabbed covid convalescent (pre vaccination).

My situation -

Covid in March 2020 and long covid since (much better in past 6 months).
Pfizer vaccine mid June and second end of August.
Booster jab booked for end of December (4 months).

Unsure whether to get the booster in the next few days at a walk in. Or wait til end of month. Or even wait longer. Obviously Omicrom spread is making me consider another jab asap...

IANAD and have no idea of your full medical history and degree of immunocompetence. If you want a booster then go get one (dose interval timing likely matters less for infected-then-vaxed from the point of view of disease). The dose will temporarily ramp up your circulating antibodies (and short-term boost homed mucosal IgA) but isn't likely to improve on the hybrid immunity that you probably already have (to VOCs and development of severe disease).

 

[2hats]

(Australia/SA) An early meta-analysis of preliminary omicron/B.1.1.529 neutralisation studies as an attempt to determine vaccine efficacy.

Six months after primary immunisation with an mRNA vaccine, efficacy for Omicron is estimated to have waned to around 40% against symptomatic and 80% against severe disease. A booster dose with an existing mRNA vaccine (even though it targets the ancestral spike) has the potential to raise efficacy to 86.2% (95% CI: 75.4-92.9) (symptomatic) and 98.2% (95% CI 90.9-99.7) (severe) against Omicron.

These estimates demonstrate good concordance with the epidemiological evidence presented in the recent UKHSA TNCC study.

DOI: 10.1101/2021.12.13.21267748.

 

[Brainaddict]

2hats based on the various studies and data youve posted, what would your take be on booster vaccine timescale for a double jabbed covid convalescent (pre vaccination).

My situation -

Covid in March 2020 and long covid since (much better in past 6 months).
Pfizer vaccine mid June and second end of August.
Booster jab booked for end of December (4 months).

Unsure whether to get the booster in the next few days at a walk in. Or wait til end of month. Or even wait longer. Obviously Omicrom spread is making me consider another jab asap...

I'm in the interesting situation of having had covid in 2020, had long covid since, got AZ first which made my LC worse, got Pfizer as second jab, then last Friday I got the Moderna booster, and on Monday I tested positive for covid by LFT, symptoms (and location in south London) suggesting it is the omicron variant. So this week I've got the Moderna jab and omicron variant doing battle in my long covid-wracked body

My symptoms are all very mild as it happens and we'll just have to see the long term effects. But I'm glad I got the booster, in part because having a jab close to catching covid is now thought to reduce long covid risk. What that means for someone already with long covid is beyond the reach of current research and statistics I suspect, but I feel glad to have got the jab anyway.

 

[Badgers]

I am not 2hats but in case my opinion is of value: get it done now ASAP.

This 100% ^

 

[Supine]

I'm in the interesting situation of having had covid in 2020, had long covid since, got AZ first which made my LC worse, got Pfizer as second jab, then last Friday I got the Moderna booster, and on Monday I tested positive for covid by LFT, symptoms (and location in south London) suggesting it is the omicron variant. So this week I've got the Moderna jab and omicron variant doing battle in my long covid-wracked body

My symptoms are all very mild as it happens and we'll just have to see the long term effects. But I'm glad I got the booster, in part because having a jab close to catching covid is now thought to reduce long covid risk. What that means for someone already with long covid is beyond the reach of current research and statistics I suspect, but I feel glad to have got the jab anyway.

Go Moderna, fuck you omicron

 

[elbows]

Big real-world molnupiravir trial has begun in the UK, although expectations for this treatment arent quite what they once were.

The first at-home treatment for Covid has been given to patients in the UK as part of a major national study.

Molnupiravir will be tested on 10,000 people at risk of serious illness in research led by University of Oxford.

Last month, the UK became the first country in the world to approve its use - a move described as a "game-changer" by health secretary Sajid Javid.

But some scientists have questioned its effectiveness after its early clinical trial results were downgraded.

Covid: First UK patients given take-at-home pill

The tablet - molnupiravir - is given twice a day to high-risk patients who have caught the virus.

www.bbc.co.uk

 

[2hats]

Valneva have released further booster data for their inactivated vaccine VLA2001. This is for a homologous boost of VLA2001 given 7-8 months after the primary vaccination course (participants aged 18-55 years).

The third (high) dose booster elicited a strong response irrespective of the primary course dosing regimen (participants received low/medium/high doses; 3/7/35 AU of antigen) resulting in an IgG geometric mean titre of 9699.3 (95%CI:8497.76-11070.71), which was 42- to 106-fold that prior to the booster, two weeks after the third dose. This was itself four times higher than the response two weeks after completing the primary series.

Evaluation of neutralisation of VOCs, including omicron, is underway.

Valneva Announces Positive Homologous Booster Data for Inactivated, Adjuvanted COVID-19 Vaccine Candidate VLA2001 - Valneva

Initial results show excellent immune response after third dose of VLA2001 administered 7 to 8 months after the second dose of primary vaccination Antibody titers increased 42- to 106-fold two weeks after booster dose vs pre-booster levels Antibody titers four-fold higher compared to two weeks...

valneva.com

 

[Supine]

Looks like J&J is going the same way as AZ. Rare side effects mean the preference will be mRNA going forward.

CDC advisory panel, concerned about rare side effects tied to J&J vaccine, gives preferential nod to mRNA shots

A panel that advises the CDC gave a rare preferential recommendation to the Covid vaccines based on messenger RNA technology on Thursday..

www.statnews.com

 

[2hats]

More omicron/B.1.1.529 neutralisation studies.

(Institut Pasteur) A live virus study looking at convalescent and vaccines sera and monoclonal antibodies. Previous findings reproduced: omicron escapes neutralisation by pretty much all but one mAb (Sotrovimab). It also escapes two dose homologous BNT162b2 and AZD1222 (at 5 months) and convalescent sera (at 6 and 12 months). It was only neutralised by three-dose BNT162b2 (at 1 month) and convalescent hybrid immunity, with single dose BNT162b2 (at 1 month).

DOI: 10.1101/2021.12.14.472630.

(NIH/Duke/Moderna/others) A mRNA-1273 pseudovirus neutralisation study. Vaccinee sera from standard (100µg) two-dose recipients (4 weeks post second dose) saw a 49 to 84-fold reduction for omicron compared to earlier D614G type. A third (half) dose (50µg) booster (administered 9 months after dose 2) restored significant neutralising capability.

DOI: 10.1101/2021.12.15.21267805.

 

[Supine]

Really good article with nice graphs. The state of play with vaccines summarised.

How COVID vaccines shaped 2021 in eight powerful charts

The extraordinary vaccination of more than four billion people, and the lack of access for many others, were major forces this year — while Omicron’s arrival complicated things further.

www.nature.com

 

[HAL9000]

Really good article with nice graphs. The state of play with vaccines summarised.

How COVID vaccines shaped 2021 in eight powerful charts

The extraordinary vaccination of more than four billion people, and the lack of access for many others, were major forces this year — while Omicron’s arrival complicated things further.

www.nature.com

Its about the level I can understand, thanks

When we get more data about omicron, it will be interesting to see how good Oxford–AstraZeneca is at stopping hospitalisation and death. Since a lot of people have received this vaccine.

 

[2hats]

Sputnik V news (no data yet). Third booster dose (of Sputnik Light) six months after original two-dose Sputnik V course claimed to neutralise omicron.

Sputnik V booster strengthens Omicron defence, developer says

A booster shot of Russia's Sputnik Light vaccine provides a stronger antibody response against the Omicron variant of COVID-19 than the two-dose Sputnik V vaccine alone, the medicine's developer said on Friday.

www.reuters.com

Putin says Sputnik V coronavirus vaccine effective against Omicron - RIA

Russia's Sputnik V coronavirus vaccine is effective against the Omicron variant, the RIA news agency cited President Vladimir Putin as saying on Friday.

www.reuters.com

 

[2hats]

Pfizer, commenting on interim trial results for paediatric BNT162b2, state that a two-dose 3µg course was apparently not as immunogenic in 2-4 year olds as previous data indicated it was in under-2s and older children. Pfizer will now investigate a three-dose course.

A clinical trial of an omicron-specific version of BNT162b2 is expected to start next month.

Pfizer says pandemic could extend to 2024, vaccine data for younger children delayed

Pfizer Inc on Friday forecast that the COVID-19 pandemic would not be behind us until 2024 and said a lower-dose version of its vaccine for 2- to 4-year-olds generated a weaker immune response than expected, potentially delaying authorization.

www.reuters.com