In the linked Twitter thread, Dr Rasmussen says that a consequence of the Ad5 vector becoming replication competent is that the E1 gene might have replaced the spike protein, rendering the vaccine ineffective.
Are there any other consequences to the Ad5 vector virus being able to replicate? Is the virus harmful to humans in any way, or does it have the potential to become harmful?
Typically Ad5 causes upper respiratory tract infections which may manifest as a cold if you’re lucky or lead to pneumonia if you’re not, although things like conjunctivitis and gastroenteritis are not unheard of. Obviously we don’t know how applicable this knowledge is to the Sputnik Ad5.
From the article: "The Ad5 variety has infected a solid proportion of the entire human race [...]. It’s believed that if you already have antibodies and T-cells primed against the Ad5 vector itself (for example) that delivery of its payload will thus be impaired, leading to a less-effective vaccination."
A reminder that "U.S. officials pushed Brazil to reject Russia’s coronavirus vaccine" [0] for political reasons.
> Under a section titled “Combating malign influences in the Americas,” the HHS report states that countries including Russia “are working to increase their influence in the region to the detriment of US safety and security.” The global affairs office coordinated with other U.S. government agencies “to dissuade countries in the region from accepting aid from these ill-intentioned states,” it says.
The concerted effort to smear the Russian vaccine is clearly the Western version of the anti-vaccine misinformation Russia has been accused of spreading. Textbook projection.
Brazilian here, but just a regular guy, I didn't dug deep into this. Anvisa (our health regulatory agency) is well stablished before current president, supposedly independant and more often considered in opposition to current government. I find it unlikely that they are fabricating a rejection and more likely they are being cientific about it.
Same here. If what they say is true, that there was viral reproduction in the vacine, theres no way is gonna pass. They schedule a session in congress with Anvisa to defend their position, and decided to not show up to the meeting. The resistance in allowing European heath agencies entering and inspecting it's labs is also a bad sign.
It is not that Anvisa is taking a political stance, but they operate under requirements of the government. The government is making it difficult for Anvisa to gather the data they need to make a decision.
This is not mutually exclusive with the findings of the Brazilian investigators. More than likely this will spur other investigations which should find the same thing if the Brazilian investigators were correct.
it reports that they in fact had the data they needed for the Pfizer vaccine in February. Sounds to me like it was just a communication issue between Anvisa & the Ministry.
For me, this really calls into question the efficacy numbers published for the Gamaleya vaccine. e.g.: The Gamaleya National Research Center of Epidemiology and Microbiology and the Russian Direct Investment Fund (RDIF) have reported that the Sputnik V Covid-19 vaccine showed a 97.6% efficacy. [0]
The Lancet didn't perform those tests, they only published the numbers provided by researchers overseeing the trials. The first author of the source paper is Denis Logunov [0] who works at the Gamaleya Research Institute [1].
The vaccine described in the paper published in The Lancet was explicitly described as using an replication deficient Ad5 vector, while the vaccine received by Brazil seems to have been replication competent.
Considering Slovakia also said that Russia did not deliver a vaccine matching the characteristics of the one in The Lancet, I think those data are basically irrelevant now.
Just a reminder that the journals don't reproduce the research before publishing the article. They only check that somewhat intelligible, somewhat new, somewhat interesting. The more serious the journal, the more strict the checks.
So the numbers are not confirmed by the Lancet, they are just published in the Lancet. It's much better than reading numbers that are published in a blog, but it's not a 100% proof that they are correct.
it's important to make clear that what make the vacine being reject was not because of this number. The problem is that they remove the dna part of the virus that allow it to replicate once injected. But in all samples that they tested, in multiple batchs, they found replicant Adenovirus, that could make people who received the vacine sick.
That said, this is not a total rejection of the vacine. This is a rejection of the batches that where going to be imported. There are plan to produce this vacine in Brazil, and this batches could be approved in the future, if they did not find the same problems.
Most scientific journals only do peer-review by sending articles to other scientists. These scientists, most of the time, only check for logical errors, and are not able to replicate the experiments.
Lancet is not "respected" after their autism fraud scandal. Re-publishing Russian state-sponsored research is not "confirming those numbers" it's just low editorial standards.
You cannot trust the Brazilian government to make this judgement. It is a policy of that government to delay the approval of vaccines as much as possible, as if there was no actual pandemic going on. Other governments around the world have analyzed the vaccine, including Argentina and Mexico, and they're using it without any problems.
If the vector is replicating, does that explain some piece of why Sputnik V is significantly more effective than the other adenovirus vector vaccines? (If that's even true, of course, since it may well not be!) Or is it simply a more effective preparation of a vaccine, due to things like the Ad5/Ad26 combination?
Unlikely, because the part of the adenovirus they delete that allows it to replicate is what they replace with the portion that generates the spike protein antigen. So if some of the adenovirus is replicating it's inherently not doing what you want it to do to produce an immune response.
Not inherently. We don't know how it's replicating.
Furthermore, this isn't even an an/or situation: the actual virus in the vial of vaccine isn't going to be 100% uniform. You could have both virus material that can and can't replicate simultaneously. The extra immune response induced by the subset that can replicate might even make the immune response against the spike protein stronger, even if your theory is correct. Remember that vaccines usually have to use adjuvants to induce a stronger immune response than the active part itself does. An actual infection could do that quite effectively.
> If the vector is replicating, does that explain some piece of why Sputnik V is significantly more effective than the other adenovirus vector vaccines?
The observed discrepancy between the delivered vaccine and the one described in the published clinical trial could, if not explain, hint at the reason the published clinical results are better than other vaccines in the same class.
To me Gamaleya is turning a thecnical decision in a political one. Thanks to mistakes and possible crimes commit by the Brazilian goverment, when rejecting other vacines, they are now being pressured in accepting this vaccine no matter what. I don't think this is how a sanitary inspection agency should act, approving things based in pure pressure.
I wonder how much we are seeing general problems with adenovirus vector vaccines (e.g. blood clotting and this manufacturing issue) only because we've never rolled a vaccine out to a large population so quickly. Regulatory agencies are likely afraid to approve any at this point, which does not bode well for other vaccines using the same technology.
Intuitively speaking, using a viral vector has inherent risks that aren’t present with mRNA or protein subunit vaccines. To the extent that the latter technologies prove effective for vaccines against various viruses, I would think viral vectors should not be a preferred technology going forward for vaccine development.
Intuitively, the risks of viral vector vaccines are well known because they have been used for at least a decade while mRNA are being used in large scale for the first time only now.
These are the first widely deployed adenovirus vector vaccine.
There have been several rounds of trials of adenovirus vectors vaccines, but they never went forward to widespread use.
Viral vector vaccines are a less new concept than mRNA vaccines, so it might be easy to see one as new and the other as traditional, but they're both new.
My intuition, given the absolute (small) magnitude of blood clots, is that it’s not a huge issue.
Except that it is, because it has people spooked. Humans, myself included, are just terrible at gauging relative risk, and it doesn’t really matter that you are way more likely to die in your car driving to get the vaccine than from any vaccine complication. You are putting this in your arm, and people find it scary when even the tiniest issues crop up.
(I’ll snark a bit here: wonder how many people who are scared of vaccines smoke cigarettes…because, in terms of risk…hoo boy.)
It's not considering the disease it's protecting against and the currently likelihood of getting it, but if we were talking a flu shot or a vaccine for some much less common disease that math would change.
I am not a virologist, but blood clotting might be related to the specific payload rather than the platform. The original SARS-CoV2 has the same property. Could it be related to the spike protein?
This preprint suggests AZ vaccine blood clotting is due to EDTA, an ingredient specific to AZ vaccine and absent in other vaccines, and is related to neither platform nor payload.
But the bigger news was that Anvisa, the Brazilian drug agency, said that every single lot of the Ad5 Gamaleya shot that they have data on appears to still have replication-competent adenovirus in it.
Sounds like a manufacturing quality-control problem. This is why you need so much sampling and analysis in drug production. It's probably fixable, but denial will not help.
Readit News
https://mobile.twitter.com/angie_rasmussen/status/1387397186...
Are there any other consequences to the Ad5 vector virus being able to replicate? Is the virus harmful to humans in any way, or does it have the potential to become harmful?
> Under a section titled “Combating malign influences in the Americas,” the HHS report states that countries including Russia “are working to increase their influence in the region to the detriment of US safety and security.” The global affairs office coordinated with other U.S. government agencies “to dissuade countries in the region from accepting aid from these ill-intentioned states,” it says.
The concerted effort to smear the Russian vaccine is clearly the Western version of the anti-vaccine misinformation Russia has been accused of spreading. Textbook projection.
[0] https://www.washingtonpost.com/world/2021/03/16/hhs-brazil-s...
Greg Lowe is a very respected commentator on all things vaccines.
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It looks like it shouldn't have been approved in the first place then.
[0]: https://www.pharmaceutical-technology.com/news/russia-sputni...
[0] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
[1] https://g.co/kgs/u6wvJ8
Considering Slovakia also said that Russia did not deliver a vaccine matching the characteristics of the one in The Lancet, I think those data are basically irrelevant now.
So the numbers are not confirmed by the Lancet, they are just published in the Lancet. It's much better than reading numbers that are published in a blog, but it's not a 100% proof that they are correct.
That said, this is not a total rejection of the vacine. This is a rejection of the batches that where going to be imported. There are plan to produce this vacine in Brazil, and this batches could be approved in the future, if they did not find the same problems.
Dead Comment
in fact, article states brazil wasn't even the first
Furthermore, this isn't even an an/or situation: the actual virus in the vial of vaccine isn't going to be 100% uniform. You could have both virus material that can and can't replicate simultaneously. The extra immune response induced by the subset that can replicate might even make the immune response against the spike protein stronger, even if your theory is correct. Remember that vaccines usually have to use adjuvants to induce a stronger immune response than the active part itself does. An actual infection could do that quite effectively.
The observed discrepancy between the delivered vaccine and the one described in the published clinical trial could, if not explain, hint at the reason the published clinical results are better than other vaccines in the same class.
> These claims are bullshit. Posting them is a disgrace.
https://blogs.sciencemag.org/pipeline/archives/2021/04/28/ru...
For the record, I believe that's the very first time I've seen him use the word "bullshit", and I've been following him for over 10 years.
Dead Comment
Well, that's the first COVID-19 vaccine the Brazilian government has rejected.
There have been several rounds of trials of adenovirus vectors vaccines, but they never went forward to widespread use.
Viral vector vaccines are a less new concept than mRNA vaccines, so it might be easy to see one as new and the other as traditional, but they're both new.
Except that it is, because it has people spooked. Humans, myself included, are just terrible at gauging relative risk, and it doesn’t really matter that you are way more likely to die in your car driving to get the vaccine than from any vaccine complication. You are putting this in your arm, and people find it scary when even the tiniest issues crop up.
(I’ll snark a bit here: wonder how many people who are scared of vaccines smoke cigarettes…because, in terms of risk…hoo boy.)
Except there are two other vaccines with no risk of bloot clots. So if you can choose, why not choose the ones that aren't linked to that?
Ofc, that mostly goes for the US and EU who have secured supply.
https://www.researchsquare.com/article/rs-440461/v1
Sounds like a manufacturing quality-control problem. This is why you need so much sampling and analysis in drug production. It's probably fixable, but denial will not help.