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Possible vaccines/treatment(s) for Coronavirus

The US FDA's vaccine advisory committee have just voted 19 to 2 (zero abstentions) in favour of recommending inclusion of a SARS-CoV-2 Omicron component for COVID-19 booster vaccines in the US.

No clear decision on what particular omicron variant sub-lineage spike this would be.

Representatives from Pfizer said it could have product available in the first week of October, whilst Moderna said it could have updated vaccine available "at large scale" in late October, early November.
 
Interesting new results from Moderna which would appear to corroborate the above work by Sigal (AHRI) on beta/omicron antigenic history.
Underscoring this further, these results are interesting, suggesting beta spike could be advantageous in a booster (perhaps not surprising given pandemic dynamics in South Africa). Possibly the ideal formulation in a polyvalent might be original WT spike plus beta plus omicron (plus perhaps the most antigenically diverse spike, determined by mapping, up to the time of production).

Results from trials of Sanofi/GSK's adjuvanted recombinant protein-based bivalent vaccine candidate (WT plus beta/B.1.351 spike), MVB.1.351.

e2a: Details in this NEJM correspondence (where comparison was made with the original WT spike formulation, MVD614):
Over the short term, heterologous boosting with the beta-adjuvanted MVB.1.351 vaccine resulted in a higher neutralizing-antibody response against the beta variant as well as against the original strain and the delta and omicron BA.1 variants than did the mRNA vaccine BNT162b2 or the MVD614 formulation. The use of new vaccines that contain beta spike protein may be an interesting strategy for broader protection against SARS-CoV-2 variants.
DOI:10.1056/NEJMc2206711.
 
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In a recent presentation Pfizer/BioNTech have indicated that they are working on a T-cell targeting pan-coronavirus vaccine to be available (presumably at least for trials) before the end of the year.
Next generation vaccine approaches aim to provide durable variant protection.
 
New clinical data for Moderna's bivalent omicron (BA.1) booster candidate, mRNA-1273.214 (50µg). One month post-administration it elicited significantly higher neutralising antibody responses against the omicron variants BA.4 and BA.5 than the original vaccine (mRNA-1273).

Moderna intend to make two bivalent booster candidates available this autumn. mRNA-1273.214 (25µg original plus 25µg BA.1 spike) for the UK/EU/Australia, and mRNA-1273.222 (25µg original plus 25µg BA.4/5 spike) for the US (to satisfy FDA requirements).
 
(Crick/Imperial/Osaka/UCL) A S2 subunit based pan-coronavirus DNA vaccine study demonstrated encouraging results in an animal model, able to neutralise the seasonal ‘common cold’ coronaviruses HCoV-OC43/HCoV-HKU1/HCoV-229E/HCoV-NL63, (original) Wuhan type SARS-CoV-2, D614G lineages from the first wave (B.1.1), alpha/B.1.1.7, beta/B.1.351, delta/B.1.617.2, omicron/B.1.1.529 and two bat coronaviruses (SL-CoV-WIV1, CoV-RaTG13).
DOI:10.1126/scitranslmed.abn3715.

Commentary:
 
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Interesting stuff but I don't know anyone who's been offered any sort of booster for months. Last one was my elderly mum who got one in about January
 
Interesting stuff but I don't know anyone who's been offered any sort of booster for months. Last one was my elderly mum who got one in about January

Everyone in Ireland over 65 or over 12 and immunicompromised were offered boosters in May and June.
And the gov is thinking of opening that up to 50 to 65 yr olds too
 
Everyone in Ireland over 65 or over 12 and immunicompromised were offered boosters in May and June.
And the gov is thinking of opening that up to 50 to 65 yr olds too

There's been talk of over 50s in the UK getting one but it hasn't happened yet. I worked at a vaccination centre in 2021 and would expect to be contacted if the centres were opening up again
 
There's been talk of over 50s in the UK getting one but it hasn't happened yet. I worked at a vaccination centre in 2021 and would expect to be contacted if the centres were opening up again

Our vacc centres have not closed. They're vacc all the time. Walk ins for those who were never vacc.
And boosters for anyone needing them or called for them.

Talk if another vacc rollout in late Sept / early Oct
 
(Various) As noted previously, eg in the Com-COV2 study: mixing of vaccines due to issues of availability/supply in Argentina has provided a nice illustration of the effective immunogenicity of a heterologous primary vaccination series. The graphical abstract says it all (almost) - that heterologous regimens are at least as, if not more effective than, a homologous series. mRNA (mRNA-1273) vaccination after other type was always most efficacious.
Heterologous combinations of SARS-CoV-2 vaccines, graphical abstract.
Two points to bear in mind: (1) this is only measuring neutralising antibodies (IgG spike), it is not an epidemiological study demonstrating efficacy against disease or efficacy of other aspects of the immune system (innate immunity, T cells, Fc/effector functions, ...), and (2) in Argentina dosing intervals were extended several weeks (eg here variously 5-11 weeks between doses) which is also known to improve immunoresponse.
DOI:10.1016/j.xcrm.2022.100706.
 
UK MHRA approves bivalent Moderna mRNA-1273.214 (WT and omicron/B.1.1.529 spikes) as a booster in 18+ year olds.
 
The JVCI have published more details of the autumn booster programme.

Notably, as well as giving the nod to bivalent Moderna mRNA-1273.214 (WT/B.1.1.529), they have now finally approved use of the Novavax (Nuvaxovid) protein subunit vaccine, NVX-CoV2373, for persons aged 18+ (note: the autumn booster campaign is for 50+, C[E]V, carers and health and social care staff) .
 
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Moderna is suing Pfizer and BioNTech (in the US and Germany), alleging various mRNA vaccine technologies patent infringement.
 
This is possibly a bit pre emptive, but it occurred to me the other day:

Being in a category of people who are offered the vaccine earlier, also means you get it when it’s not really known how well that vaccine will work against whichever variant is dominant by the time the rollout is going. The data on that gets collected after enough people have had that vaccine whilst immersed in whatever flavour viral soup this country is having that season.

With the booster last winter, omicron appeared around when I might have had some protection from that vaccine. I booked to go to a few gigs and planned some social stuff. Then everything changed. And by the time things settled down and the waning effect was understood, I was well outside of that period. It seems like people who were offered the booster in spring of 2022 were better able to benefit from it.

It’s pretty selfish / self serving to look at it this way but I am wondering if am offered the next booster in the early stage of the rollout this autumn, should I actually hang on for a few weeks / months to see what kind of benefits it’ll give. It doesn’t seem like predicting that effect is going to be possible.

Dunno. Just thinking out loud really.
 
It’s impossible to predict anything with this virus though isn’t it?

Eg… Say there’s a new variant about in the UK come October. Say you had a booster vaccination and then were exposed to that version of the virus a couple of weeks later and the recent vaccine helped prevent you getting sick from it. If you were exposed to that variant again a few months later and that vaccine’s effects had waned, the previous infection wouldn’t make any difference? That’s my understanding of what omicron has been like.
 
The analysis they can do about those things tends to paint a rather broad picture that offers some clues that have significance when it comes to the whole population level, and related stuff such as overall hospital demand, and planning what frequency of vaccination they should attempt.

And there is a relationship between the overall risk picture and what that means for individuals, but its not really possible to translate the overall risk assessments into a guide as to the risks to specific individuals at a particular moment in time. There are people who on paper might have anticipated being well protected via optimal number and timing of doses, who were still killed by this virus during the theoeretical windows of maximum protection. And this was not a surprise. Plenty of those people would have theoeretically been at greater overall covid risk for well known reasons, such as their age or specific medical conditions, but still this is not a perfect guide, the reality isnt quite that neat for every individual, only for the overall numbers when we look at large numbers of people and can identify patterns.

When it comes to waning the picture is also not as neat and simple as it may be in some peoples minds. We can see patterns where the waning protection against infection is more obvious than the waning of protection against hospitalisation, and where the waning of protection against death is weaker still. And so far we have not allowed very large periods of time to pass between vaccination doses for the people more at risk due to age, so we havent allowed these signals to be magnified to a much greater extent. And experts and professionals dont find it easy to all come to the same conclusions about what the optimal or necessary dosing schedules are. eg some think that continued boosters beyond the first ones are a big waste if given to huge numbers of people, they suspect that protection will generally remain good enough for several years. In some of these areas we will probably get to find out, in others the risks will not be taken that would enable us to find out.

And of course yes changes to the virus also further complicate this picture. Omicron caused authorities convern because it always takes time to truly discover how the theoretic risks of evasion from vaccine protection compared to the actual evasion seen in practice. Perhaps its fair to say that Omicron worst case scenarios did not materialise when it came to immune escape from protection against serious illness and death, and that boosters with non-Omicron-specific vaccines were enough to offset a big chunk of these bad consequences. In terms of its ability to evade immunity from infection and mild disease, clearly Omicron was bad enough to change the game on that front, to give us many waves with really huge number of people getting infected. And such things caused all bets to be off in terms of some assumptions they hoped to be able to get away with when it came to how many waves we might get per year, and the size of those waves, and how often individuals might expect to get infected. Stuff that has implications for ongoing pressure on health services, even when they've managed to dodge a large public debate about that in this country this year.
 
In terms of your thinking out loud about whether to try to manipulate the timing of when you get a vaccine dose, there are so many potential factors, lots of luck is involved, and there are no guarantees that what you and authorities will eventually discover will tell you that you were right to delay, it might just as likely reveal that you should have got another vaccine ASAP. And certain things might be revealed that the authorities wont be able to act upon during that vacination cycle anyway, eg if it turns out that a different sort of vaccine would be better, but it wont be available in time to protect masses of people against that wave. Or things that are down to random chance, such as if various different types of vaccines are in the system at the same time, but you have no choice as to which one happens to be available at the vaccination centre you happen to attend on a particular day.

I'm a simple case of a middle aged person whose only been offered 3 doses so far. I may as well describe what happened to me in terms of luck and timing for those first three doses, as just one example of how this stuff can play out:

I dragged my heels a bit when it came to booking first vaccine, because I was keen for more nerdy detail to emerge, and because I could effectively hide from the virus in the meantime, and could avoid being a potential vector of transmission to any relatives that were more at risk than me. That initial deliberate delay of some weeks happened to, by chance, enable me to end up getting a dose of Pfizer rather than Oxford Astrazenica. But this wasnt planned, it just turned out that way because by the time I booked my first vaccination they had decided not to give the Oxford vaccine to people a bit younger than me, and people in that age group were allowed to book fro the very first time on the very same day I happened to finally get round to booking.

By the time I could get my second dose, there was some early evidence that perhaps quite a long gap between first two doses had benefits for the amount of protection that may be afforded. So I was going to wait the fill 12 weeks. But then some things happened which made the authorities reduce that gap, and there were concerns about a resurgence in the virus, so I decided to go along with that and reduce the gap.

The same thing happened with my third dose. I was going to leave the full gap, especially as I still wasnt exposing myself to risky situations. But then concerns about Omicron loomed large on the authorities radar, and I decided to do what they wanted and get my third dose in December rather than dragging things out till early the next February.

Timing issues that I had relatively little control over for all 3 of those doses is that my periods of theoretical best protection were out of sync with other family members due to differences in age and medical conditions between us. eg my parents and brother were eligible for vaccination far ahead of me, so by the time I got a dose they had already entered a period where waning concerns had grown. Hopefully this was more of an issue for first few doses, and magnitude of potential waning/differences in protection against severe disease and eath isnt as great once 2+1 doses were done, but cannot really be sure that we'll never end up totally out of sync in a way that has significant implications ever again. Although as the authorities plan currently stands, I dont get another dose this winter and the rest of them do, and if this plan sticks then we wont find out if this plan had any big mistakes in it for some time, will either find out with much hindsight or they will get clues that make them change the plan (eg age cutoff) again at some point.

When making those latter timing decisions I had to balance various things including optimal protection, protection timing compared to next wave timing, timing the authorities preferred, ease of availability of booking slots and vaccine system capacity, what timing seemed like the best for broader society, what timing my family preferred. And people sometimes have other practical timing considerations too, eg having particular events on the calendar for which they didnt want to be suffering any post-vaccination symptoms, or wanted to feel like they were most protected for.
 
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Oh and one unknown at this stage is the extent to which the updated Omicron-specific vaccine will actually be available for the vaccination programme this winter. Its been approved, but its far from clear what the supply and logistics will be like, what proportion of people will end up being given that version, whether any fancy criteria are used eg prioritising certain groups for that version, or whether its ends up more down to random chance as to who gets what. Or indeed how much difference it ends up making.
 
Oh and one unknown at this stage is the extent to which the updated Omicron-specific vaccine will actually be available for the vaccination programme this winter. Its been approved, but its far from clear what the supply and logistics will be like, what proportion of people will end up being given that version, whether any fancy criteria are used eg prioritising certain groups for that version, or whether its ends up more down to random chance as to who gets what. Or indeed how much difference it ends up making.

Supply isn't a problem apparently, everyone will get the omicron-specific vaccine. They already have millions of doses of the Moderna bivalent vaccine with millions more on the way. It seems the BBC have put some articles out implying otherwise by saying stuff like this:

"The NHS says Moderna's new bivalent vaccine will be used for autumn boosters, 'subject to sufficient supply'. The UK is the first country to approve the dual vaccine. However, health officials say people should take whichever booster they are offered, as all vaccines provide protection against becoming severely ill or dying from Covid."

However there's no actual anticipated supply problems, so I wouldn't take routine arse-covering as implying something else
 
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Cheers for the info. I expect the arse-covering came from the relevant authorities and the BBC just ran with it.

For example the following stuff was included in announcements, presumably because they dont want people quibbling or delaying their vaccination if they arent offered the updated vaccine for any logistical reason:

NHS England:


The NHS will offer people the new next generation bivalent vaccine where appropriate and subject to sufficient supply being made available to the NHS.

The JCVI and MHRA have stressed that the original vaccines also continue to provide great protection and people should come forward regardless of vaccine offered.

Government statement in relation to England:


As we cannot predict which variants of COVID-19 will be circulating this winter, the Joint Committee on Vaccination and Immunisation (JCVI) have concluded that both types of vaccine can be used in adults, and that no one should delay vaccination to receive combination vaccines. So you will be offered the right vaccine for you at the right time.

From NHS England » NHS to roll out variant busting booster jab from September ahead of winter

JCVI advice was pretty conservative in terms of them saying they didnt have a huge amount of data about how much better the new vaccine will be compared to the older ones. I might quote some of that stuff in a bit but part of the aim is not to make the older vaccines sound undesirable. But its pretty standard stuff, its what we would expect from them.
 
Cheers for the info. I expect the arse-covering came from the relevant authorities and the BBC just ran with it.

For example the following stuff was included in announcements, presumably because they dont want people quibbling or delaying their vaccination if they arent offered the updated vaccine for any logistical reason:

NHS England:




Government statement in relation to England:




From NHS England » NHS to roll out variant busting booster jab from September ahead of winter

JCVI advice was pretty conservative in terms of them saying they didnt have a huge amount of data about how much better the new vaccine will be compared to the older ones. I might quote some of that stuff in a bit but part of the aim is not to make the older vaccines sound undesirable. But its pretty standard stuff, its what we would expect from them.

Yes exactly, the BBC didn't inquire behind the scenes to determine what the actual supply situation looked like, so someone reading their articles might think that there was an actual intention to offer the old vaccines to some people. On the other hand the PA etc seem to have checked: "The new bivalent booster has been developed to target both the original strain of the virus and the Omicron variant. The NHS does not expect supply to be an issue and all of those eligible are expected to receive the variant-busting jab."
 
Any initial doubts about available supply of different types of vaccine could also have led to the resulting practical implications being compounded by the fact that the August JCVI statement placed quite a lot of emphasis on simplicity in addition to timeliness. They seemed to be leaning towards sticking with the original vaccine if enough doses of bivalent vaccine to completely cover this seasons programme had not been assured, although in that respect they were also totally hedging their bets even if it meant somewhat overriding the option they describe as 'desirable', of using just one sort of vaccine. They were covering all possibilities I suppose, with the further get out of 'operational considerations', and again emphasised what advice the public should receive, that timeliness trumps type of vaccine.

Timeliness of vaccination is more important than the type of booster vaccine used. The key priority of the autumn programme should be for eligible individuals to be offered a booster vaccine dose to increase their immunity against severe COVID-19 (hospitalisation and death) ahead of winter 2022 to 2023, as described in the previous advice of 15 July 2022.

Simplicity is central to an efficient vaccination programme. Deployment of a single type of vaccine throughout the autumn booster programme promotes simplicity and is therefore desirable. If sufficient doses of mRNA bivalent Original ‘wild-type’/Omicron BA.1 vaccine become available to complete the autumn booster programme, JCVI considers that it is expedient to aim to offer authorised bivalent vaccines throughout the autumn programme, subject to operational considerations. Where substantial delays might be incurred in deploying a bivalent vaccine, the principle of timeliness should take priority and an alternative UK-approved booster vaccine offered, such as a monovalent Original ‘wild-type’ mRNA vaccine. Individuals offered vaccination should be advised that timely boosting is desirable to increase protection over the winter, and therefore to accept whichever booster vaccine is offered.

 
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A couple of studies of relevance to booster vaccines.

(NIH) A study which indicates that B-cell responses to booster vaccines are impeded by recent infection. Vaccinated persons with no prior infection, or persons infected 180 days or more prior to boosting produced greater immunoresponses (IgG NAbs*) than those boosted within 180 days of an infection (or, possibly similarly, repeatedly boosted at short intervals). Likely this is related to the 'blunting' anticipated by Crotty et al and an illustration of the advantage of permitting adequate time (6-9 months) for full affinity maturation (here described as allowing sufficient time for various B cell types to return to optimal resting states in order to best respond to a booster dose).
DOI:10.1101/2022.08.30.22279344.
(* Insert usual warning that other measurements of immunity are available.)

(UCT/Karolinska/Imperial/ETH/others) This small study might suggest cross-immunity for BA.2.75 acquired from BA.1/BA.2 is better than that acquired from BA.4/BA.5. This might make for some difference in outcomes between eg EU v US (BA.1 v BA.5 bivalent late-2022 booster) if BA.2.75[.x] proves to be as aggressive as it might appear.
New cases per day in. the UK of BF.7, BA.2.75.1, BA.2.75.2, BA.2.75.5 compared with BA.5.2, the main recent wave driver (base on genomic data from COG-UK).
DOI:10.1016/S1473-3099(22)00524-2.
 
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