COVID COVID-19 Vaccine Progress: Are We Ready for Rollout in Australia?

[Ygggdrasil]

From memory of 'a few days ago', Los Angeles published this priority list:

Medical workers
1) First responders (paramedics, fire, [police?])
2) Nursing Homes, residents and staff
3) High-risk members of the public (co-morbidities and age >65)
4) High-risk members of the public (co-morbidities)
5) High-risk members of the public (age>65)
6) General public

Items 4) and 5) may have been combined with the 'or' operator.

(further research turned up these)
Here is a link to the California Dept of Health recommended priorities:
https://www.cdph.ca.gov/Programs/CI...-Vaccine-During-Phase-1A-Recommendations.aspx

The California Governor announced:
https://calmatters.org/health/coronavirus/2020/12/california-priorities-first-covid-vaccines/
https://infogram.com/california-vaccine-priorities-1hxj48pp5qrkq2v

The US National Academies of Medicine published guidelines for allocating the Coronavirus vaccine. These are just guidelines, however, and states have the final say in which groups they decide to prioritize:

 

[kyphysics]

If there truly were a shortage, I'd personally be okay with not vaccinating prisoners themselves, but vaccinating the staff first. Maybe leave the prisoners to Phase 4?

 

[kyphysics]

If given a choice, which of the two major ones - Pfizer of Moderna - would you take?

Has there been any thought of someone taking both (if supplies are abundant and we can "afford to" at some point)?

 

[bhobba]

I recall reading somewhere about a protocol in which a placebo is NOT used, and instead an existing medication or vaccine is used.

That is the view of Professor Borody on when you should use double blind studies ie when comparing the efficacy of two different treatments. He thinks the moral issues of those that get a pacebo and hence have a greater risk are too great (remember before stage 3 it has passed stage 1 and 2 so we know it does work to some extent). But there is the reverse argument - there is a chance those getting the treatment do worse than the placebo. He is a very strong proponent of it as detailed in the video I gave before that for convenience I will repost:
https://covexit.com/professor-thomas-borody-interview-part-2/

I tend to agree, but consider the issue much more nuanced than if you push double blind studies where it is not appropriate (of course in his opinion) you need to go back to medical school (of course he is half joking - but still it shows how strongly he holds his view on the matter).

Thanks
Bill

 

[bhobba]

Totally separate issue/question: Why isn't every able pharma company on the planet now manufacturing the Pfizer or Moderna vaccine?

Because the accelerated process that does not compromise safety is to carry out large scale manufacturing in parallel with stage 3 studies. The Oxford vaccine for example is much cheaper than Pfizer and probably Modernia, but India is already manufacturing 1 billion doses in anticipation of approval. It seems to have a similar efficacy (to be conformed). So what do you do - if proven effective and safe throw out a billion doses? Besides the Pfizer vaccine has logistic issues with distribution due to how cold it must be stored at. Here in Aus we are making nearly 60 million doses of the Oxford vaccine to be deployed once stage 3 trials are completed to the satisfaction of our regulatory bodies, who also want to see how it goes overseas like in India before passing it. That is expected to be about March. The production of the vaccine is expected here in Aus to be finished end this year - early next year. Then we will manufacture a similar amount of the Novavax vaxine immediately after - it may be better - we do not know yet. Why not manufacture the Pfizer vaccine? CSL, our vaccine manufacturer, does not have the capability to make it.

Thanks
Bill

 

[Ygggdrasil]

Johnson & Johnson published data from the phase 1/2 trial of their vaccine candidate: https://www.nejm.org/doi/full/10.1056/NEJMoa2034201

The J&J vaccine is a viral vector vaccine, like the Oxford-AstraZeneca vaccine, though it uses a different viral vector than the Oxford-AstraZeneca vaccine. The vaccine would be easier to store than the mRNA vaccines (Pfizer-BioNTech and Moderna) as it can be stored at normal refrigerator temperature for up to three months. Notably, the trial is testing a one-dose versus two-dose administration of the vaccine.

In the study, participants had neutralizing antibodies, measured in a unit called a geometric mean titer, of 224 to 354, on day 29 after their first vaccine dose; those levels reached 288 to 488 by day 57. These levels could be enough to produce immunity. But there was a big benefit to giving the participants a booster dose. It doubled or tripled their levels of neutralizing antibodies. The question is whether the antibody levels induced by the first dose are indeed enough, or if there are other types of immunity spurred by the vaccine that lead to protection.

“Just because it’s higher in neutralizing response doesn’t necessarily mean it’s more efficacious,” said Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. “It may be that the immune response induced by the first dose is enough and that more is not necessarily better.”

The answer to the question, of course, will come from Phase 3 clinical trial results. Said Carlos del Rio, a distinguished professor of medicine at the Emory University School of Medicine: “The proof is in the pudding.”

https://www.statnews.com/2021/01/13...r-jjs-one-dose-covid-vaccine-will-measure-up/

However, because the study is still only an early stage clinical trial, the study reports only on antibody levels and does not measure the actual efficacy of the vaccine in preventing disease. Efficacy data will await completion of phase 3 clinical trials (which are currently underway).

Unfortunately, these positive phase 1/2 data are tempered by news that production of the J&J vaccine is two months behind schedule, so even if approved soon, the vaccine may not be able to make an impact for a few more months:

Johnson & Johnson has fallen behind on production of its Covid-19 vaccine, a delay that could put it as much as two months behind schedule, a person briefed on the matter told POLITICO.

The company had originally pledged to deliver 12 million doses by the end of February, with plans to reach 100 million over the next four months.

But Johnson & Johnson has since warned officials that it could take until the end of April to catch up to its original projections, the person briefed on the matter said.

https://www.politico.com/news/2021/01/13/johnson-johnson-vaccine-production-458941

 

[stefan r]

...

Unfortunately, these positive phase 1/2 data are tempered by news that production of the J&J vaccine is two months behind schedule, so even if approved soon, the vaccine may not be able to make an impact for a few more months:

We need 8 or 16 billion vaccines. A large portion of them need to be available in places that do not have cold storage options. If immunity is temporary we need 8 (or 16) billion per year for a few years. Its not O.K. to vaccinate a few rich old people and then pretend everything is fine.

Waiting for the virus to mutate would be rash.

The pharmaceutical companies might make more money if the virus festers and we have to keep re-vaccinating every year for the rest of our lives. Eradication is much cheaper in the long run.

 

[Laroxe]

I was reading through the thread and thought there were a few issues worth highlighting, perhaps the most important being the speed of change in our knowledge base. The earlier link to an article in Nature, on Vaccines in development and published in September 2020, predated the recent explosion in information about both the vaccines and the immune response.
I'm not sure why the author found it necessary to describe traditional development pathways for vaccines as this was already widely discussed in the media and in fact many of these issues have effectively been consigned to history. Perhaps what is more important is the views expressed on the immune response, particularly to SARS-CoV2 might quickly be following them. At the moment it appears that generating a robust antibody response is not difficult, but we still don't know the levels required to achieve effective protection nor the changes that occur over time. A great deal of the emphasis in research has switched to the T cell responses which hold the promise of long term protection.
There is also a discussion about the rather strange idea of sterilising immunity, this really refers to the way in which a vaccine reduces transmission. As we have a reasonable idea about the infection risk presented by individuals at various stages of infection, preventing disease has a marked effect on the possible length of time a person might shed the virus and the amount of virus they shed. There is always the possibility of transmitting a virus to a non immune person, even if its simply by surface contamination just like its possible for an immune individual to become reinfected, there is more than the level of immunity to consider. We will only know the effect of the vaccine on transmission after some time, but it will have an effect.
In terms of vaccine development it is still possible to conduct trials particularly as so many areas still have no access to vaccines, this of course will become harder over time. However the phase 3 trials which need the highest numbers may still be possible in areas with low levels of vaccine acceptance.
We do need the vaccine trials to continue, its very unlikely that the very high levels of effectiveness reported in the early trials will stand the test of time, we don't know which ones will be best. There are also new vaccines that specifically target parts of the immune system, like tissue immunity in the nasopharynx, these may not require injections and might impact on transmissibility.
I just thought it was fascinating to see the rapid changes in the science and perhaps consider how political and social issues impact on its application. Remember a huge amount of money was invested in developing our vaccine production facilities and this is still going on, drug companies can't simply switch production.

 

[PeroK]

Its not O.K. to vaccinate a few rich old people and then pretend everything is fine.

What evidence do you have that in the UK, for example, the vaccine is being given only to a few rich old people?

https://en.wikipedia.org/wiki/COVID-19_vaccination_programme_in_the_United_Kingdom

 

[Jarvis323]

What evidence do you have that in the UK, for example, the vaccine is being given only to a few rich old people?

https://en.wikipedia.org/wiki/COVID-19_vaccination_programme_in_the_United_Kingdom

There have been complaints by the WHO, and other groups about vaccines being 'hoarded' by rich countries.

The People's Vaccine Alliance says nearly 70 lower-income countries will only be able to vaccinate one in 10 people.

https://www.bbc.com/news/health-55229894

At least 90% of people in 67 low income countries stand little chance of getting vaccinated against Covid-19 in 2021 because wealthy nations have reserved more than they need and developers will not share their intellectual property, says the People’s Vaccine Alliance, which includes Amnesty International, Frontline AIDS, Global Justice Now, and Oxfam.1

“Unless something changes dramatically, billions of people around the world will not receive a safe and effective vaccine for Covid-19 for years to come,” said Anna Marriott, Oxfam’s health policy manager.

Rich countries with only 14% of the world’s population have bought up 53% of the eight most promising vaccines, the alliance said, including all of the Moderna vaccine doses expected to be produced over the next year and 96% of the Pfizer-BioNTech vaccine doses.

https://www.bmj.com/content/371/bmj.m4809

WHO's director said only 25 vaccine doses have been provided in a single poor country, while over 39 million doses have been administered in nearly 50 richer nations

https://www.kare11.com/article/news...-old/507-b56e5785-b679-4512-9a31-de4071c7f408

 

[PeroK]

There have been complaints by the WHO, and other groups about vaccines being 'hoarded' by rich countries.

It's difficult to know what to make of those links.

It says that the richest countries make up only 14% of the world's population. China has about 18% of the world's population and is the second largest economy. So I imagine a) China doesn't count as a rich country and b) China is not planning to vaccinate its citizens?

India, likewise, has 18% of the world's population, has the 5th largest ecomony and is likewise not considered rich? As fas as I am aware, India plans a full vaccination programme.

Also, the vaccines should go, surely, to the countries most affected by COVID. Many of the world's poorest countries have largely escaped COVID: all of Africa, except RSA, for example.

The USA has over 20% of total COVID deaths. So, it wouldn't seem particularly unfair if 20% of the first batch of vaccines went to the USA.

To take another example: Vietnam has a population of nearly 100 million but only 1500 cases and 35 deaths; compared to the UK with 3.6 million cases and almost 100,000 deaths. It would seem bizarre to me if the first batch of vaccines went to Vietnam, rather then to the UK, where they are needed.

The vaccines are going where they are needed most, surely?

 

[Jarvis323]

It's difficult to know what to make of those links.

It says that the richest countries make up only 14% of the world's population. China has about 18% of the world's population and is the second largest economy. So I imagine a) China doesn't count as a rich country and b) China is not planning to vaccinate its citizens?

India, likewise, has 18% of the world's population, has the 5th largest ecomony and is likewise not considered rich? As fas as I am aware, India plans a full vaccination programme.

Also, the vaccines should go, surely, to the countries most affected by COVID. Many of the world's poorest countries have largely escaped COVID: all of Africa, except RSA, for example.

The USA has over 20% of total COVID deaths. So, it wouldn't seem particularly unfair if 20% of the first batch of vaccines went to the USA.

To take another example: Vietnam has a population of nearly 100 million but only 1500 cases and 35 deaths; compared to the UK with 3.6 million cases and almost 100,000 deaths. It would seem bizarre to me if the first batch of vaccines went to Vietnam, rather then to the UK, where they are needed.

The vaccines are going where they are needed most, surely?

Good points.

 

[Ygggdrasil]

Also, the vaccines should go, surely, to the countries most affected by COVID.

This creates something of a perverse incentive, though. All countries are affected by the pandemic and most have had to put into place restrictions and lockdowns to prevent the spread. Do we reward the countries that have done the worst job of containing the pandemic by awarding them the most vaccines? Countires that have avoided putting into place strict COVID restrictions often made these choices for economic reasons. Should countries that enacted strict and effective COVID restrictions take a double hit to their economies (from strict COVID restrictions and late access to vaccines) compared to the countries that chose to looser restrictions?

 

[PeroK]

This creates something of a perverse incentive, though. All countries are affected by the pandemic and most have had to put into place restrictions and lockdowns to prevent the spread. Do we reward the countries that have done the worst job of containing the pandemic by awarding them the most vaccines? Countires that have avoided putting into place strict COVID restrictions often made these choices for economic reasons. Should countries that enacted strict and effective COVID restrictions take a double hit to their economies (from strict COVID restrictions and late access to vaccines) compared to the countries that chose to looser restrictions?

Undoubtedly China has been one of the most successful countries in containing the virus. I'll let you write to your Senator and suggest that the USA postpones its vaccination programme while all the available vaccines are shipped to China, as a reward for having contained the virus so successfully.

 

[PeroK]

Good points.

As far as I can tell, India is manufacturing huge quantities of the vaccines and - by whatever means - has made provision for itself. Oxfam is completely ignoring this, when it says that we've ordered 53% of all vaccines. That must exclude the vaccines that India is keeping for itself.

In addition, China has two potential vaccines, which again are excluded from the picture painted by Oxfam. And, these are available for export to other Asian countries, covering huge populations.

Ultimately, it seems like the usual phoney, politicised BS. The West has bought 53% of something, but that something is definitely not the world's total vaccine supply.

This piece from the Guardian gives a much more plausible and balanced picture:

https://www.theguardian.com/world/2...countries-rush-to-access-covid-vaccine-supply

 

[Laroxe]

The complaint that vaccines are going preferentially to the wealthy countries presents an interesting problem.
Of course it has been the wealthy countries that have invested huge sums of money in vaccine development and risked equally huge sums on funding pre-approval production facilities. Without this there would be no complaints of unfairness because there would be no vaccine to distribute. Western governments have also provided the WHO with funds to support vaccine availability. Its interesting that the WHO is already complaining about money even though it has started to receive batches of vaccine, which the end users are still waiting for. It seems that the game of passing the blame around for inefficiency has become global in record time.
Of course governments try to act in the best interests of their own citizens, that's their job, if there was no advantage how could they justify spending the money. In many ways it is the fact that many producers are quite deliberately making the vaccine available to others and at reduced cost, that's unusual.

 

[Ygggdrasil]

Agreed. Current vaccine distribution is simply based on which countries have been able to afford the vaccines and fund their development (though some less wealthy countries are getting vaccines because the companies are willing to provide them a discount or because of the aforementioned WHO fund to provide vaccines for ~70 extremely poor countries). There is little evidence to support the idea that there is some higher moral justification for vaccine distribution (e.g. "The vaccines are going where they are needed most, surely").

 

[PeroK]

There is little evidence to support the idea that there is some higher moral justification for vaccine distribution (e.g. "The vaccines are going where they are needed most, surely").

It's not higher moral justification, it's necessity. The UK is in desperate need of a vaccine. As much as any country on the planet.

PS We have the highest death rate of any country at the moment, so I'd like to hear who you think needs it more?

You can criticize what others are doing - so let's hear your worldwide rollout plan. To which countries would you send the vaccines and why?

 

[russ_watters]

Do we reward the countries that have done the worst job of containing the pandemic by awarding them the most vaccines?

Yes. We're trying to save the most lives here, aren't we?

Countires that have avoided putting into place strict COVID restrictions often made these choices for economic reasons. Should countries that enacted strict and effective COVID restrictions take a double hit to their economies (from strict COVID restrictions and late access to vaccines) compared to the countries that chose to looser restrictions?

Who chose looser restrictions for economic reasons? It appears to me that the most significant factor affecting the spread of COVID has been connectedness vs isolation.

Oxfam

Oh. Oxfam.

 

[Laroxe]

It's not higher moral justification, it's necessity. The UK is in desperate need of a vaccine. As much as any country on the planet.

PS We have the highest death rate of any country at the moment, so I'd like to hear who you think needs it more?

You can criticize what others are doing - so let's hear your worldwide rollout plan. To which countries would you send the vaccines and why?

To be fair I don't think there was any criticism implied, I think that Ygggdrasil was simply making the point that when there is a shortage of any resource its the people who can pay the price that get first choice. Its the countries that paid for the development and ordered/ paid for the vaccines first, that control who gets them. The decisions are not driven by moral considerations, though they play some part. Even the WHO doesn't have a global rollout plan, in fact few countries even have adequate national plans, there are simply to many variables to take into account that no single group has control over.
Remember hunger remains a widespread problem even though globally there is no shortage of food, but the producers still want paying. This then reintroduces the economic effects of of the epidemic, its not just a matter of human connectedness, its much broader. Its the connectedness of work, the movement of produce, payment etc that supports most of our lives, without this Covid would be irrelevant, the UK can't even feed itself. Restricting movement and activities that reduce spending has a massive effect on our ability to deal with any problem, reducing personal contact reduces risk at the micro level but has the potential to reduce the resources we need to manage the pandemic at every other level.

 

[stefan r]

...

Also, the vaccines should go, surely, to the countries most affected by COVID. Many of the world's poorest countries have largely escaped COVID: all of Africa, except RSA, for example.

The USA has over 20% of total COVID deaths. So, it wouldn't seem particularly unfair if 20% of the first batch of vaccines went to the USA.

To take another example: Vietnam has a population of nearly 100 million but only 1500 cases and 35 deaths; compared to the UK with 3.6 million cases and almost 100,000 deaths. It would seem bizarre to me if the first batch of vaccines went to Vietnam, rather then to the UK, where they are needed.

The vaccines are going where they are needed most, surely?

We can attack your reasoning. If we wanted to minimize the number of fatalities we would vaccinate in order to prevent covid19 cases. Places like New Jersey or North Dakota have considerable partial herd immunity. Week 11 or 12 is usually the end of flu season in the USA. It takes weeks for the vaccine to be fully effective. The covid19 infection rate plummeted in May of 2020. Australia is still a mostly virgin population, they are going into the new flu season, and the new strains appear spread more quickly.

I'm well aware that my neighbors would get violent if I publicly suggested Africa should get the vaccine before the Northeast USA.

Within the USA or New Jersey the distribution is still debatable. A rich 60 year old is safer if the case rate drops by 95% than he would be with a vaccine. We could vaccinate gas station attendants, store clerks, and food service workers. Cut off the infection routes.

What evidence do you have that in the UK, for example, the vaccine is being given only to a few rich old people?

https://en.wikipedia.org/wiki/COVID-19_vaccination_programme_in_the_United_Kingdom

I did not say that so I do not need to defend it. Clipping my post changed the meaning. I said exterminating the virus requires more vaccines than there are people on Earth. That is a total production target. Who gets a vaccine first is another issue.

In general suppose I make a statement like "it is wrong to beat your spouse with a lead pipe". That is not condoning beating your spouse with a stick. It is not condoning beating your spouse without a stick. It is not condoning beating anyone else with a lead pipe or anything other tool or no tool. It is also not a claim that I have any evidence for or any belief that you have ever abused your spouse.

the production targets need to be ramping up and they need to continue ramping up. If CEOs of pharmaceutical companies can figure out how to expand production of vaccine from 0 per day to 1 million per day then they can apply that skill and continue ramping up production to 50 million per day. If they don't have a plan to supply it globally then we should just take the technology and give it to people who will. It is better to persuade the CEOs to do the right thing.

What evidence do you have that in the UK, for example, the vaccine is being given only to a few rich old people?

https://en.wikipedia.org/wiki/COVID-19_vaccination_programme_in_the_United_Kingdom

I had not looked at it before. Your wikilink does say it is going to a bunch of old people in England. The queen got hers. It looks like Wales is getting shafted. Only 543 total people got a second shot. Are they poor?

 

[PeroK]

I had not looked at it before. Your wikilink does say it is going to a bunch of old people in England. The queen got hers. It looks like Wales is getting shafted. Only 543 total people got a second shot. Are they poor?

Believe it or not (and I suspect you won't) everyone in the UK is entitled to the vaccine on an equal basis. There is no rich and poor about it.

You're free, of course, to have your personal beliefs about the UK, our people, our government and our health service. But, your statement "It looks like Wales is getting shafted." shows that your criticisms are irrational ramblings, born of prejudice and ignorance.

 

[Laroxe]

If we wanted to minimize the number of fatalities we would vaccinate in order to prevent covid19 cases.

Luckily that isn't how it works. The great majority of deaths occur in the elderly with the risk clearly associated with age. If this group can be protected by vaccination and this is targeted by age the number of deaths will reduce very quickly and well before the disease is controlled by population level immunity. Groups identified as potential "super spreaders" like health care workers are also early targets for vaccination.
Many countries have vaccination plans that are designed to achieve a reduction in deaths as the first priority.
Remember that the production of the biological products used in vaccination is a complex process, if anything goes wrong at any stage large amounts of vaccine may need to be discarded. Then increasing production often involves building new facilities or taking others offline to upgrade them, something both Pfizer and AstraZeneca are doing. However the short period of interruption in supply has already lead to complaints, even from places that haven't gotten around to authorising the use of that vaccine.
Really we don't know if we will ever achieve the level of herd immunity needed to control this disease, nor do we know if it might be possible to eliminate it, its all guesswork until we have the data, which continues to be collected, but this involves money as well

 

[Ygggdrasil]

If we wanted to minimize the number of fatalities we would vaccinate in order to prevent covid19 cases.

I agree with @Laroxe here. Researchers have used mathematical models to study which groups should get priority in order to reduce deaths, the groups most at risk of mortality or the groups at most risk of spreading the disease. While they find that vaccinating younger people first does minimize transmission, it does a worse job at minimizing mortality than vaccinating older people first:

“Almost no matter what, you get the same answer,” says Harvard epidemiologist https://www.hsph.harvard.edu/marc-lipsitch/. Vaccinate the elderly first to prevent deaths, he says, and then move on to other, healthier groups or the general population. One recent study modeled how Covid-19 is likely to spread in six countries—the U.S., India, Spain, Zimbabwe, Brazil, and Belgium—and concluded that if the primary goal is to reduce mortality rates, adults over 60 should be prioritized for direct vaccination. The study, by Daniel Larremore and Kate Bubar of the University of Colorado Boulder, Lipsitch, and their colleagues, has been published as a preprint, meaning it has not yet been peer reviewed.

https://www.scientificamerican.com/...math-on-who-should-get-a-covid-vaccine-first/

Here's a link to the pre-print manuscript cited:
Model-informed COVID-19 vaccine prioritization strategies by age and serostatus
https://www.medrxiv.org/content/10.1101/2020.09.08.20190629v3

Abstract:

Limited initial supply of SARS-CoV-2 vaccine raises the question of how to prioritize available doses. Here, we used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20-49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults over 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact. While maximum impact prioritization strategies were broadly consistent across countries, transmission rates, vaccination rollout speeds, and estimates of naturally acquired immunity, this framework can be used to compare impacts of prioritization strategies across contexts.

 

[russ_watters]

Places like New Jersey or North Dakota have considerable partial herd immunity...

Within the USA or New Jersey the distribution is still debatable.

I pointed out the apparent partial herd immunity in other threads and got considerable push-back. But regardless of the cause of differing infection rates, you could prioritize based on likely existing immunity and current infection rates, or even death likelihood. But that's very complex and has a lot of practical problems/unknowns associated with it. Of the top of my head:

1. Current infection rates aren't future infection rates (when people become immune).
2. Unknown overall population immunity.
3. Unknown individual immunity (you could exclude people who have previously tested positive).
4. Unknown transmission possibility when vaccinated.
5. Inter-state travel.
6. How, exactly, do we mix this all together to arrive at an allocation/proportion?

Per #3 I think I would prefer excluding people who have previously tested positive, and maybe even add antibody testing to that.

 

[Ygggdrasil]

On the topic of Coronavirus vaccine progress, Merck has discontinued development of two of its vaccine candidates on the basis of poor performance in phase 1 clinical trials:

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the company is discontinuing development of its SARS-CoV-2/COVID-19 vaccine candidates, V590 and V591, and plans to focus its SARS-CoV-2/COVID-19 research strategy and production capabilities on advancing two therapeutic candidates, MK-4482 and MK-7110. This decision follows Merck’s review of findings from Phase 1 clinical studies for the vaccines. In these studies, both V590 and V591 were generally well tolerated, but the immune responses were inferior to those seen following natural infection and those reported for other SARS-CoV-2/COVID-19 vaccines.

https://www.merck.com/news/merck-di...f-two-investigational-therapeutic-candidates/

The two candidates were viral vectored vaccines, one using a weakened measles virus and the other using a vesicular somatitis virus (VSV) vector. The VSV vector had previously been used to produce a successful Ebola vaccine. Researchers had hoped that these strategies, which employed viral vectors that could replicate inside the body, could provide a long-lasting, one-dose vaccine.

The next best candidates for additional vaccines are the Johnson and Johnson adenoviral vectored vaccine (where phase 3 trial results are expected to be released shortly) and the Novavax protein subunit vaccine (which had promising phase 1/2 trial data and may have phase 3 trial data within a month).

See also https://www.statnews.com/2021/01/25...two-covid-19-vaccines-and-focus-on-therapies/

 

[Ygggdrasil]

Novavax released a press release of https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3 of its vaccine in the UK and South Africa. Notably, these two trial locations are areas where new lineages of the Coronavirus have emerged recently (B.1.1.7 in the UK and B.1.351 in South Africa), and they found differing effectiveness of their vaccine in the two locations:

A Covid-19 vaccine from Novavax proved nearly 90% effective in preliminary results from a key clinical trial in the United Kingdom, the company said, but in a separate trial appeared far less effective against a new variant of the coronavirus that was first identified in South Africa.

In its 15,000-volunteer U.K. trial, Novavax said, the vaccine prevented nine in 10 cases, including against a new strain of the virus that is circulating there. But in a 4,400-volunteer study in South Africa, the vaccine proved only 49% effective.

https://www.statnews.com/2021/01/28...ffective-but-far-less-so-against-one-variant/

These results are roughly consistent with some of the emerging science about the variants. The mutations in the B.1.1.7 variant in the UK don't seem to affect immunity to the virus, whereas it is thought that mutations in the B.1.351 variant in South Africa (in particular the E484K mutation) may aid in evading immunity. The E484K mutation is also present in the P.1 variant identified in Brazil that seems to be causing large outbreaks in areas that were thought to have high infection rates during the first wave of the virus in early 2020.

The Novavax vaccine is a protein subunit vaccine, which is a more traditional vaccine technology than the mRNA vaccines developed by Pfizer-BioNTech and Moderna or the adenoviral vector vaccines being developed by Oxford-AstraZeneca and Johnson & Johnson. Because it is based on more widely used technologies, it might be possible for larger scale production of this vaccine than the others. Unlike the mRNA vaccines (which require the vaccine to be stored frozen), the Novavax vaccine is stable at normal refrigerator temperatures, which could aid in distribution.

 

[Ygggdrasil]

Johnson & Johnson has released preliminary results from the phase 3 clinical trial of its single-shot COVID-19 vaccine:

Johnson & Johnson said Friday that its single-dose Covid-19 vaccine reduced rates of moderate and severe disease, but the shot appeared less effective in South Africa, where a new Coronavirus variant has become common.

Overall, the vaccine was 66% effective at preventing moderate to severe disease 28 days after vaccination. But efficacy differed depending on geography. The shot was 72% effective among clinical trial volunteers in the U.S, but 66% among those in Latin America, and just 57% among those in South Africa. Though markedly below the levels seen with the first two authorized Covid-19 vaccines, those rates are above the thresholds originally set by the U.S. Food and Drug Administration for a vaccine to be considered useful.

The vaccine reduced severe disease alone by 85%, and prevented Covid-related hospitalization or death, Johnson & Johnson said.

https://www.statnews.com/2021/01/29...-effective-a-weapon-but-not-a-knockout-punch/

The J&J vaccine uses an adenoviral vector to deliver spike protein DNA inside of cells, and the lower efficacy of the vaccine (~70%) is similar to that seen of another adenoviral vectored vaccine (the Oxford-AstraZeneca vaccine). Lower efficacy against new variants in South Africa and Latin America is consistent with emerging science that these variants contain mutations (specifically the E484K mutation) that changes the shape of the virus such that antibodies that recognize the original spike protein have a harder time neutralizng the mutant spike proteins (see discussion in the post above).

Because it requires only a single dose and the vaccine is stable at normal refrigerator temperatures, the J&J vaccine would probably be the easiest to distribute among the major vaccine candidates.

 

[Ygggdrasil]

The Lancet recently published a peer-reviewed interim analysis of phase 3 clinical trial data in Russia of the "Sputnik-V" vaccine produced by the Gamaleya Institute.

Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext

Between Sept 7 and Nov 24, 2020, 21 977 adults were randomly assigned to the vaccine group (n=16 501) or the placebo group (n=5476). 19 866 received two doses of vaccine or placebo and were included in the primary outcome analysis. From 21 days after the first dose of vaccine (the day of dose 2), 16 (0·1%) of 14 964 participants in the vaccine group and 62 (1·3%) of 4902 in the placebo group were confirmed to have COVID-19; vaccine efficacy was 91·6% (95% CI 85·6–95·2). Most reported adverse events were grade 1 (7485 [94·0%] of 7966 total events). 45 (0·3%) of 16 427 participants in the vaccine group and 23 (0·4%) of 5435 participants in the placebo group had serious adverse events; none were considered associated with vaccination, with confirmation from the independent data monitoring committee. Four deaths were reported during the study (three [<0·1%] of 16 427 participants in the vaccine group and one [<0·1%] of 5435 participants in the placebo group), none of which were considered related to the vaccine.

The Gamaleya vaccine is an adenoviral-vector based vaccine, like the Oxford-AstraZeneca vaccine and the Johnson & Johnson vaccine. However, the Gamaleya vaccine (92% efficacy) seems to offer greater efficacy than either the Oxford-AstraZeneca vaccine (62%) or the single dose Johnson & Johnson vaccine (66%). This could be due to the fact that the vaccine employs a heterologous prime-boost strategy in which the two doses of the virus are delivered by two different adenoviral vectors (rAd26 and rAd5). This avoids the possibility that the body could develop immunity to the adenoviral vector which would lower the effectiveness of the second shot if delivered using the same vector.

--------------------------------

AstraZeneca also published a new non-peer-reviewed pre-print with some additional analysis of their vaccine:
Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268

The paper suggests that the vaccine could be more effective with a longer delay between prime and boost doses (3 months vs 6 weeks) and that a one-dose regime could also be effective, though the numbers from the trial are still small to show a statistically significant difference between the different conditions. The results could be related to the issues of vector-induced immunity discussed above.

 

[Astronuc]

My wife was asking about the different vaccines and how they different, how they work, why m-RNA, and so on. I found a few articles:

Comparing the Covid-19 vaccines developed by Pfizer, Moderna, and Johnson & Johnson
https://www.statnews.com/2021/02/02...eloped-by-pfizer-moderna-and-johnson-johnson/
JnJ are awaiting approval for their vaccine, apparently hoping for this week.

I was trying to find if this article had been posted on PF - How nanotechnology helps mRNA Covid-19 vaccines work
https://www.statnews.com/2020/12/01/how-nanotechnology-helps-mrna-covid19-vaccines-work/

Meanwhile, there are issues on the production and distribution of the vaccines. I posted in the GD thread on the COVID-19 Coronavirus Containment Efforts, but repeat here.

Why the vaccine rollout in the U.S. has been slower than expected
https://www.pbs.org/newshour/show/why-the-vaccine-rollout-in-the-u-s-has-been-slower-than-expected

Supply shortages and delays leave Europe’s vaccination campaign in crisis
https://www.pbs.org/newshour/show/s...-leave-europes-vaccination-campaign-in-crisis

Twenty-six million vaccine doses were delivered to the European Union by mid-February, with around two-thirds of them used. That's just a fraction of the E.U.'s population of 450 million.

All three of the vaccines authorized for use, Moderna, BioNTech/Pfizer and Oxford-AstraZeneca, have cut deliveries in the first quarter. Pfizer has not yet delivered around 10 million doses that were due in December, leaving the bloc a third short.

Rates of production at European sites across the board have been unable to meet demand. Ursula von der Leyen, European Commission president, and German herself, has admitted mistakes were made.

I heard somewhere a comment about the supply of nano-lipids to the effect that the demand was underestimated. It was one of several challenges in the supply chains for the vaccine producers.