Additional vaccines: Novavax, Janssen and Valneva

[cormanr7]

There is a distinct lack of vaccine availability at the moment but some further entrants may partially alleviate that from mid year on. Novavax has reported a 89% efficacy against preventing COVID in participants in its UK trial (does not mention if this includes mild/asymptomatic cases). An ongoing trial in South Africa showed a rather lower protection against the SA mutant of ca 60%. Teesside in the UK has been chosen as one of the production sites. https://www.bbc.com/news/uk-55850352 The Novavax vaccine differs from the mRNA, viral vector and inactivated virus vaccines in that it is a protein vaccine. Spike protein from the virus is incorporated into nanoparticles and injected with an adjuvant.

Data from Janssen (from Johnson & Johnson) on their large phase III trial is expected next week. This is a viral vector vaccine (a la AZ and Sputnik) but can possibly be limited to a single shot which would be a huge advantage. It is widely expected that emergency use authorization might be given end of Feb/early March in the UK and US.

Finally, Valneva has started production of their inactivated virus vaccine in Livingston (Scotland), though their trials have only just started. If successful, deliveries are not expected till the end of the year.https://www.bbc.com/news/uk-scotland-edinburgh-east-fife-55840567.

 

 

 

[mommysboy]

UK seems to be becoming a world leader in the creation and pioneering  of covid19 treatments and vaccines.  The Novavax (USA)  and Valneva (FR) vaccines are particularly intriguing for opposite reasons- the former being advanced technology that can be used in a practicable way, while the latter uses the oldest method, but will hopefully produce effective and safe results, perhaps unlike others produced elsewhere.  I'm just wondering if the mRNA vaccines will be somewhat crowded out due to their inherent expense and logistical problems.  Hats off to Novavax in particular.

Edited January 29, 2021 by mommysboy

[mommysboy]

J and J data has been released. Now, I think this is a good vaccine and would be happy to take it, since it prevents serious disease just like the others. 

 

But the 66% efficacy it quotes, surely isn't true in the sense we are familiar with since it discounts mild infection.  If we used that measure on the AZ jab then we'd likely be talking much higher.  The J and J is being touted as a one-shot vaccine and there is some truth in that, but again the AZ vaccine is much the same, and its strategy has been roundly criticized.  It's funny that while AZ jab was panned in the USA, the J and J is being hailed as a game changer and an effective shield. Suddenly, the selling it next to the mRNA vaccines isn't so difficult after all- lol! Or perhaps it's just not foreign.

 

https://www.bloomberg.com/news/articles/2021-01-29/j-j-single-dose-vaccine-provides-strong-shield-against-covid-19

[rabas]

2 hours ago, mommysboy said:

J and J data has been released. Now, I think this is a good vaccine and would be happy to take it, since it prevents serious disease just like the others. 

 

But the 66% efficacy it quotes, surely isn't true in the sense we are familiar with since it discounts mild infection.  If we used that measure on the AZ jab then we'd likely be talking much higher.  The J and J is being touted as a one-shot vaccine and there is some truth in that, but again the AZ vaccine is much the same, and its strategy has been roundly criticized.  It's funny that while AZ jab was panned in the USA, the J and J is being hailed as a game changer and an effective shield. Suddenly, the selling it next to the mRNA vaccines isn't so difficult after all- lol! Or perhaps it's just not foreign.

 

https://www.bloomberg.com/news/articles/2021-01-29/j-j-single-dose-vaccine-provides-strong-shield-against-covid-19

Science tells a somewhat different story. J&J is a one shot vaccine and was developed as such. The real reason for the lower that expected efficacy is they ran a broad trial in many battle ground countries against newer mutations.  In particular, South Africa where 95% of all cases are now the 501Y.V2 variant (aka B.1.351). This reduced their numbers. See:

 

COVID variants throw J&J vaccine a curveball, lowering efficacy to 66%.

 

So J&J's excellent (real world, challenging) trial against the worst of the worst, compared to AZ's somewhat botched trial showing 62% efficacy in Brazil against older strains. How low would AZ's efficacy drop against newer strains? Could it drop below 50%? See:

 

Medical-press: Vaccine wars escalate as new antibody escape variants raise the bar.

 

AZ's trial highlighted issues with multiple dose adendovirus delivery vectors, which can interfere via the immune system. This was a known issue and several companies sought ways around it.

 

mRNA: Never an issue         (mRNA code)

J&J: Use a single dose.       (DNA code)

Sputnik-5: cleverly used 2 different viral vectors. (cDNA code)

 

Edited January 30, 2021 by rabas

[cormanr7]

1 hour ago, rabas said:

Science tells a somewhat different story. J&J is a one shot vaccine and was developed as such. T

 

Yes, but I am pretty sure that JJ soon found out that the one shot strategy did not result in fantastic data.  So mid Nov. they announced a second large trial (ENSEMBLE 2) where 30,000 participants will receive two shots (as per their website https://www.jnj.com/johnson-johnson-initiates-second-global-phase-3-clinical-trial-of-its-janssen-covid-19-vaccine-candidate ). 

Talking about the AZ trial it has escaped notion that 80% of participants were health professionals (I think that also goes some way to explain why not many elderly people were tested) so not really a representative sample (if there is such a thing in phase III trials). It will be interesting to see some detailed data from Janssen.

Finally, a new phase 1/2 trial using AZ vaccine as first- and Sputnik as second shot is supposed to start next month  https://www.reuters.com/article/us-health-coronavirus-astrazeneca-russia-idUSKBN29O1BA

 

[mommysboy]

All the early vaccines were only tested against the older strains. It is said that it is relatively easy to tweak the formula.  One day in the lab.  But of course then they have to undergo a small trial and then be produced. 

 

I'm not sure what the point is about health professionals.  I would have thought these people are actually exposed to much higher viral loads, so inoculating them against infection actually promotes more of a challenge.

 

The only reliable data from the Astrazeneca trial involved what we now know is a sub-optimal dosing strategy.  It would now appear that spacing the doses to up to 12 weeks provides higher efficacy. (I really think AZ have represented this vaccine badly so far).

 

In judging these vaccines it is important to ditch the notion of a silver bullet solution. That would only be possible if the whole world got inoculated roughly at the same time. As we have seen virus strains produce variants, or new strains come along. Moreover, immunity is likely to wane after a year or so.  In my view the more humble vaccines may prove to be more agile, and certainly less expensive, since jabs are likely to be a yearly thing.

 

I think Novavax likely trumps all, however. 

 

Finally it bears saying again- all these vaccines are winners because they appear to prevent serious infection.

[mommysboy]

3 hours ago, rabas said:

Science tells a somewhat different story. J&J is a one shot vaccine and was developed as such. The real reason for the lower that expected efficacy is they ran a broad trial in many battle ground countries against newer mutations.  In particular, South Africa where 95% of all cases are now the 501Y.V2 variant (aka B.1.351). This reduced their numbers. See:

 

COVID variants throw J&J vaccine a curveball, lowering efficacy to 66%.

 

So J&J's excellent (real world, challenging) trial against the worst of the worst, compared to AZ's somewhat botched trial showing 62% efficacy in Brazil against older strains. How low would AZ's efficacy drop against newer strains? Could it drop below 50%? See:

 

Medical-press: Vaccine wars escalate as new antibody escape variants raise the bar.

 

AZ's trial highlighted issues with multiple dose adendovirus delivery vectors, which can interfere via the immune system. This was a known issue and several companies sought ways around it.

 

mRNA: Never an issue         (mRNA code)

J&J: Use a single dose.       (DNA code)

Sputnik-5: cleverly used 2 different viral vectors. (cDNA code)

 

 

'Could it drop below 50%? See:'

 

Yes, but is that 50% against all grades of infection (AZ), or 50% against moderate and severe infection (JJ)?

 

Surely there is a big difference!  We do know AZ had no hospitalizations at all.

 

The vaccines are mostly the same.  You could just as well call the AZ vaccine one shot too.  Or give the JJ jab in two shots.  In fact I wonder if this is the real reason behind the sudden change in the UK strategy.

Edited January 30, 2021 by mommysboy

[partington]

6 hours ago, mommysboy said:

 

I'm not sure what the point is about health professionals.  I would have thought these people are actually exposed to much higher viral loads, so inoculating them against infection actually promotes more of a challenge.

 

 

I'm sorry to nitpick, but "viral load" does not mean what you think it means.  I have seen newspapers, TV reporters and even GPs get this wrong.

 

It does not mean "initial infective dose", how much virus it has taken to infect you. It is nothing to do with loading you up with virus to catch the disease.

 

It is a measure of how strongly the disease is progressing- how much and how fast the virus is replicating in your body after infection has occurred. It is measured in terms of numbers of viral particles in your blood or body fluids at different stages of the disease.

 

Of course people with high viral loads -people at the peak of the course of the disease that has infected them- will be shedding lots of virus and so be at their most infectious, and maybe this is where the confusion has arisen.

 

Here is a quote from a New Scientist article explaining this:

 

"The average number of viral particles needed to establish an infection is known as the infectious dose. We don’t know what this is for covid-19 yet, but given how rapidly the disease is spreading, it is likely to be relatively low – in the region of a few hundred or thousand particles, says Willem van Schaik at the University of Birmingham, UK.

 

 

Viral load, on the other hand, relates to the number of viral particles being carried by an infected individual and shed into their environment. “The viral load is a measure of how bright the fire is burning in an individual, whereas the infectious dose is the spark that gets that fire going,” says Edward Parker at the London School of Hygiene and Tropical Medicine."

Read more: https://www.newscientist.com/article/2238819-does-a-high-viral-load-or-infectious-dose-make-covid-19-worse/#ixzz6l2fTfNqe

Edited January 30, 2021 by partington

[shdmn]

11 hours ago, mommysboy said:

J and J data has been released. Now, I think this is a good vaccine and would be happy to take it, since it prevents serious disease just like the others. 

 

But the 66% efficacy it quotes, surely isn't true in the sense we are familiar with since it discounts mild infection.  If we used that measure on the AZ jab then we'd likely be talking much higher.  The J and J is being touted as a one-shot vaccine and there is some truth in that, but again the AZ vaccine is much the same, and its strategy has been roundly criticized.  It's funny that while AZ jab was panned in the USA, the J and J is being hailed as a game changer and an effective shield. Suddenly, the selling it next to the mRNA vaccines isn't so difficult after all- lol! Or perhaps it's just not foreign.

 

https://www.bloomberg.com/news/articles/2021-01-29/j-j-single-dose-vaccine-provides-strong-shield-against-covid-19

When you break out the non-African non-UK numbers it has similar efficacy to the mRNA vaccines. The mRNA vaccines have not yet been tested against the African and UK strains.

Edited January 30, 2021 by shdmn

[shdmn]

8 hours ago, cormanr7 said:

Yes, but I am pretty sure that JJ soon found out that the one shot strategy did not result in fantastic data.  So mid Nov. they announced a second large trial (ENSEMBLE 2) where 30,000 participants will receive two shots (as per their website https://www.jnj.com/johnson-johnson-initiates-second-global-phase-3-clinical-trial-of-its-janssen-covid-19-vaccine-candidate ). 

Talking about the AZ trial it has escaped notion that 80% of participants were health professionals (I think that also goes some way to explain why not many elderly people were tested) so not really a representative sample (if there is such a thing in phase III trials). It will be interesting to see some detailed data from Janssen.

Finally, a new phase 1/2 trial using AZ vaccine as first- and Sputnik as second shot is supposed to start next month  https://www.reuters.com/article/us-health-coronavirus-astrazeneca-russia-idUSKBN29O1BA

 

There is an ongoing AZ Phase 3 trial being done properly in the US with 2 shots and a wide age range.  Those numbers are due in March and should clear up a lot of the uncertainty from their botched Phase 3 trial done elsewhere.

 

The 2 shot J&J trial was started before the results of this one shot trial. It was not started because of poor results.  These results are actually quite good imo.  If you take out the African data it's similar efficacy to the mRNA vaccines which were not tested against the African strain.

Edited January 30, 2021 by shdmn

[mommysboy]

20 minutes ago, shdmn said:

There is an ongoing AZ Phase 3 trial being done properly in the US with 2 shots and a wide age range.  Those numbers are due in March and should clear up a lot of the uncertainty from their botched Phase 3 trial done elsewhere.

 

The 2 shot J&J trial was started before the results of this one shot trial. It was not started because of poor results.  These results are actually quite good imo.  If you take out the African data it's similar efficacy to the mRNA vaccines which were not tested against the African strain.

 

But the efficacy chosen only relates to prevention against moderate and severe infection.

 

The other vaccines counted mild infections too.

 

So the JJ figure is not as it seems.

[mommysboy]

1 hour ago, partington said:

I'm sorry to nitpick, but "viral load" does not mean what you think it means.  I have seen newspapers, TV reporters and even GPs get this wrong.

 

It does not mean "initial infective dose", how much virus it has taken to infect you. It is nothing to do with loading you up with virus to catch the disease.

 

It is a measure of how strongly the disease is progressing- how much and how fast the virus is replicating in your body after infection has occurred. It is measured in terms of numbers of viral particles in your blood or body fluids at different stages of the disease.

 

Of course people with high viral loads -people at the peak of the course of the disease that has infected them- will be shedding lots of virus and so be at their most infectious, and maybe this is where the confusion has arisen.

 

Here is a quote from a New Scientist article explaining this:

 

"The average number of viral particles needed to establish an infection is known as the infectious dose. We don’t know what this is for covid-19 yet, but given how rapidly the disease is spreading, it is likely to be relatively low – in the region of a few hundred or thousand particles, says Willem van Schaik at the University of Birmingham, UK.

 

 

Viral load, on the other hand, relates to the number of viral particles being carried by an infected individual and shed into their environment. “The viral load is a measure of how bright the fire is burning in an individual, whereas the infectious dose is the spark that gets that fire going,” says Edward Parker at the London School of Hygiene and Tropical Medicine."

Read more: https://www.newscientist.com/article/2238819-does-a-high-viral-load-or-infectious-dose-make-covid-19-worse/#ixzz6l2fTfNqe

 

Thank you for your very educative post.  I think in this case then I meant infectious dose: my contention is health workers are more likely to encounter a higher initial infective dose.

[shdmn]

21 minutes ago, mommysboy said:

 

But the efficacy chosen only relates to prevention against moderate and severe infection.

 

The other vaccines counted mild infections too.

 

So the JJ figure is not as it seems.

The 89% is the most important number because that is the one that keeps you out of the hospital.  It's important to again point out that this test was done at a different point in time where the virus is more widespread.   Where people are being exposed to a higher viral load and there are more mutations.  If the mRNA vaccines were tested again today they could also have lower efficacy.  So it's not all black and white.

 

Anyways, it's not like shopping for a car.  Experts say get which ever vaccine you can as soon as you can because they all do a good job preventing serious illness and that's the most important thing.

Edited January 30, 2021 by shdmn

[mommysboy]

11 hours ago, shdmn said:

The 89% is the most important number because that is the one that keeps you out of the hospital.  It's important to again point out that this test was done at a different point in time where the virus is more widespread.   Where people are being exposed to a higher viral load and there are more mutations.  If the mRNA vaccines were tested again today they could also have lower efficacy.  So it's not all black and white.

 

Anyways, it's not like shopping for a car.  Experts say get which ever vaccine you can as soon as you can because they all do a good job preventing serious illness and that's the most important thing.

 

It is a baptism of fire in these trials.  Far more variants than in earlier trials.

 

I see your point- it's the one I've mostly been making on these forums, but why can't AZ for instance use this measure?  

 

I agree the bottom line is all these vaccines appear to be highly effective.

 

Maybe all vaccines should produce 3 figures- mild, moderate, severe.  And efficacy should be the middle number.

 

I'd still like to know what the real trial efficacy is - 50% I'd guess.  And I imagine AZ will be roughly the same on one shot.

 

[rabas]

Additional information about Novavax and J&J vaccine performance against the South African 501.V2 (aka B,1,351) strain. The effects are becoming clearer.

 

https://www.reuters.com/article/us-health-coronavirus-vaccines-variant/fresh-data-show-toll-south-african-virus-variant-takes-on-vaccine-efficacy-idUSKBN29Z0I7

[mommysboy]

20 minutes ago, rabas said:

Additional information about Novavax and J&J vaccine performance against the South African 501.V2 (aka B,1,351) strain. The effects are becoming clearer.

 

https://www.reuters.com/article/us-health-coronavirus-vaccines-variant/fresh-data-show-toll-south-african-virus-variant-takes-on-vaccine-efficacy-idUSKBN29Z0I7

 

Bit of a frightener- but JJ vaccine still prevented most serious infection- 'J&J’s vaccine was 89% effective at preventing severe disease in South Africa.'

 

I can see all these jabs becoming even more like the flu jab. 

[cormanr7]

3 hours ago, mommysboy said:

 

Bit of a frightener- but JJ vaccine still prevented most serious infection- 'J&J’s vaccine was 89% effective at preventing severe disease in South Africa.'

 

 

Reading the small print, there was a rather disconcerting observation in the placebo group of the Novavax SA-trial: 30% had been infected previously but the infection rate was approx the same as in those that had not had COVID previously. This suggested that natural immunity build up against earlier variants did not protect against reinfection by the 'SA-variant'.

However, there are no details at the moment, an alternative/additional explanation might be that immunity had (partially) waned by the time that the trial started. This seems to be unlikely in that reinfections in other parts of the world seem rather low.