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Possible vaccines/treatment(s) for Coronavirus

J&J/Janssen AD26.CoV2.S, a single dose viral vector vaccine, has been approved by the US FDA. (Can be stored at 2-8C for up to 3 months.)
 
Why the dip at the end?
Lack of data returns. Consider how few participants there are by then. The correct statement is that efficacy improves up to 56 days and then beyond that confidence is currently poor.

e2a: The FDA vaccine EUA packages are very thorough, provide a lot of answers that are otherwise missing from the public domain and leave one in little doubt where the remaining question marks are. It's a shame one for AZD1222 hasn't been submitted yet.
 
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Here a study into vaccine effectivity specifically against the P.1 variant. A (VSV) pseudovirus was constructed which featured all 10 point mutations found in the P.1 variant. The neutralising effect of several monoclonal antibodies, convalescent plasma and both BNT162b2 and mRNA-1273 mediated sera (from 22 donors, variously collected a week or more after the second dose where manufacturer posology had been followed) was tested against this. Convalescent plasma was found to be almost seven times less effective against P.1 than earlier wild type SARS-CoV-2. mRNA vaccine sera were found to be 2-3x less effective against P.1 than earlier wild type (BNT162b2 having a slight edge). These results are consistent with the P.1 related findings of the (first) two studies reported previously in post #1253.
P1neutred.png
DOI: 10.1101/2021.03.01.433466.

By way of comparison, reduction in effectiveness of vaccine sera against B.1.351 was, using the same approach (by the same team), previously found to be around 7-9 fold for both mRNA vaccine sera (again, BNT162b2 yielding the least ground), though note that this was observed to be a 10-13 fold reduction in assays with authentic virus.
B1351neutred.png
DOI: 10.1101/2021.01.25.428137.

These studies clearly highlight the additional degrees of immune escape that B.1.351 has over P.1 (and both have over B.1.1.7 and earlier wild type).
 
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Reductions in efficacy of the intervention: variously selected antibodies, convalescent sera (ie the previously infected), vaccine sera (from vaccinated persons) under consideration. This is usually expressed as either how many more multiples of each is required to reach the same level of neutralisation of the virus, or as factors of dilution to achieve the same or as some relative measure of the level of various antibodies - it varies with the study. Essentially one is just looking at the factor (sometimes orders of magnitude - note log scales) of effectiveness comparing how whatever it is that is being tested performs relative to the action of the same against an earlier variant. From above - see the relative drop in 'performance' (follow the green arrows) of Moderna (left), Pfizer (right) vaccines (technically the vaccine mediated sera retrieved from vaccinated persons) against B.1.1.7 ('UK/Kent' variant) and B.1.351 ('SA' variant) compared to an earlier variant (the main variant with the D614G mutation was that that dominated cases over summer last year across Europe) - though in this particular case this isn't the 'real' virus variant of each but an artificial copy of each constructed in the lab (the upper panels of the original figure illustrate that the performance against 'real world' virus is reduced yet further still) .
annB1351neutred.png
 
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2hats thanks for that explanation. I am starting from a low level of understanding, I don't even know what the Y axis represents. I see that the plots in pink on the left don't align well with the plots in black in the middle and even less well with the plots in orange on the right. Is it as simple as that, they don't align therefore they don't have effect?

And is there a reason they haven't tested the Oxford AZ also?
 
I don't even know what the Y axis represents.
1/(amount required to neutralise the [pseudo]virus).
I see that the plots in pink on the left don't align well with the plots in black in the middle and even less well with the plots in orange on the right.
Not align but maps to.
Is it as simple as that, they don't align therefore they don't have effect?
No. That more of each (= lower on plot) is required to achieve the same degree of neutralisation of the [pseudo]virus.
And is there a reason they haven't tested the Oxford AZ also?
Because it doesn't have [emergency] regulatory approval where they are ie the US (so pick one or more of: there is no one conveniently available to collect sera from, or it is harder to collect such, or of little immediate interest to them).
 
Moderna have prepared and shipped re-engineered booster vaccines, mRNA-1273.351, for phase I trials against B.1.351, along with a multivalent, mRNA-1273.211, which combines the original and B.1.351 targeted vaccines.

Novavax have also tweaked NVX-CoV2373 for new variants and are completing animal trials with it. They plan to submit a package for their original vaccine to gain UK MHRA approval later this month.
 
And yet again, at least the eighth study (I think I have counted) indicating a strong immune response in previously infected individuals ('Asymptomatic' and 'Symptomatic' US healthcare workers) after a single vaccine dose. Here such recipients of mRNA vaccines (BNT162b2 and mRNA-1273) exhibited very strong IgG antibody (left) and live virus neutralisation responses (right), initially beginning to peak 1 week after the single dose and much stronger than seronegatives' responses ('Ab negative') by two weeks.
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DOI: 10.1001/jama.2021.3341.
 
A study of cross-reactivity between variants (using earlier types, B.1.1.7, B.1.351, all live virus) found that, whilst antibodies can be high, cross-neutralisation is poor. This suggests that multivalent vaccines would be the appropriate approach.
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Evd1bUBXYAQrH9R

DOI: 10.1101/2021.03.01.433314.
 
Indian vaccine manufacturer Bharat Biotech's COVAXIN (inactivated whole virus, two dose regime, 28 days apart, storage at 2-8C) reported as having 80.6% efficacy against symptomatic COVID-19, two weeks after the second dose, in phase III trials (25800 participants, 18-98 years of age). This trial ran from late November to present, during the latter period of which it appears B.1.1.7 has become largely dominant (though data is sparse) on a background of earlier 19A/B clades and D614G.
 
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The studies on seropositives and dosing keep rolling in. Here a small study comparing SARS-CoV-2 naive and recovered, again illustrating the swift, strong jump in response of both antibodies and memory B cells in seropositives after a single dose (and little change after the second dose). Separately they note a (not unexpected) suggestion of poorer memory B cell response with advancing age.

NR-mRNA.png NR-memB.png
DOI: 10.1101/2021.03.03.21252872.
 
Updated report on a previously highlighted study, confirming the significant and rapid response in seropositives after one mRNA dose and side effects at greater frequencies than seronegatives.
nejmc2101667_f1.jpeg

DOI: 10.1056/NEJMc2101667.

And again (the tenth study, I think now, coming to a similar conclusion) - seropositives large immune response after a single dose of BNT162b2 - a study of 642 Spanish healthcare workers. Relative IgG responses to spike at 3 weeks after first dose for seronegatives and variously classified seropositives (the more severe the episode of COVID-19, the greater the response):
3wkspostbnt162b2.png
DOI: 10.1101/2021.03.08.21253065.

Study number 11 - here 22 participants - looking at T and B cell responses, IgG, IgM and neutralising antibodies titres in seropositives after a single dose of BNT162b2. You can, by now, guess the outcome.
DOI: 10.1101/2021.03.05.21252590.
 
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Similar to an earlier study focussed on mRNA-1273 dosing, here BNT162b2 also found to be effective at lower doses in adults aged 19-55. A two dose 10μg regimen elicits a comparable response to the standard 30 μg dose for binding antibodies, viral neutralisation, cytokine profiles, and CD4, CD8 expansion. Similarly, a single dose 10μg regimen or a two dose 1μg regimen equals or exceeds the immunogenicity of a single 30 μg dose. Obvious implications for vaccine supply, logistics, costs, potentially side effects.
DOI: 10.1101/2021.03.06.21253058.
 
Moderna have prepared and shipped re-engineered booster vaccines, mRNA-1273.351, for phase I trials against B.1.351, along with a multivalent, mRNA-1273.211, which combines the original and B.1.351 targeted vaccines.
Amendment to phase II trials have now begun (booster study for previous recipients), separate phase I trails to commence shortly.
 
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Updated report on a previously highlighted study, confirming the significant and rapid response in seropositives after one mRNA dose and side effects at greater frequencies than seronegatives.
nejmc2101667_f1.jpeg

DOI: 10.1056/NEJMc2101667.

And again (the tenth study, I think now, coming to a similar conclusion) - seropositives large immune response after a single dose of BNT162b2 - a study of 642 Spanish healthcare workers. Relative IgG responses to spike at 3 weeks after first dose for seronegatives and variously classified seropositives (the more severe the episode of COVID-19, the greater the response):
View attachment 258219
DOI: 10.1101/2021.03.08.21253065.

Study number 11 - here 22 participants - looking at T and B cell responses, IgG, IgM and neutralising antibodies titres in seropositives after a single dose of BNT162b2. You can, by now, guess the outcome.
DOI: 10.1101/2021.03.05.21252590.
Blimey.
I suppose I could have caught it during my 16 weeks at work between June and October - I have to say I was distinctly disturbed that masks weren't mandated till very late ...
 
On age-dependent immune response to vaccination and in particular the importance of second dose and timing thereof...
179 volunteers serological analysis 17-19 days after first dose of BNT162b2 and 17 days after second dose. Seropositives screened (by identifying nucleocapsid specific antibodies). Clear illustration of immunosenescence.
agedepBNT162b2.png
DOI: 10.1101/2021.03.03.21251066.

Particularly important in the light of UK dosing schedules (especially mRNA based vaccines) and the shift in risk of vaccine escape (see, for example, DOI: 10.1126/science.abg8663). Notably where one has a partially vaccinated 'part immune' elderly cohort along with a large, more mobile, younger cohort; a potential issue highlighted in this fairly simple mathematical modelling from the Joint UNIversities Pandemic and Epidemiological Research consortium, which is the basis of this New Scientist article:
 
New Pfizer press release, summarising their analysis of results thus far from real world use of BNT162b2 in Israel. They claim 97% efficacy against symptomatic and severe COVID-19, and death. Additionally, they claim 94% efficacy against asymptomatic SARS-CoV-2 infections. Both measured at two weeks after the second dose, as per manufacturer's standard dosing interval.
 
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