Brazil Rejects the Gamaleya Vaccine

https://blogs.sciencemag.org/pipeline/archives/2021/04/28/brazil-rejects-the-gamaleya-vaccine

by Clewza313 • 5 years ago

230 94 5 years ago

blogs.sciencemag.org

hardtke• 5 years ago

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.

ummonk2• 5 years ago

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.

627467• 5 years ago

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.

xvilka• 5 years ago

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?

sanxiyn4• 5 years ago

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.

https://www.researchsquare.com/article/rs-440461/v1

nikolay• 5 years ago

The adenoviruses themselves are known to cause blood clotting for years and were questioned long ago as being a good vector.

toast0• 5 years ago

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.

perardi• 5 years ago

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.)

Exmoor3• 5 years ago

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.

nottorp2• 5 years ago

My intuition, given the absolute (small) magnitude of blood clots, is that it’s not a huge issue.

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.

temporalparts2• 5 years ago

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]

[0] https://www.pharmaceutical-technology.com/news/russia-sputni...

vbezhenar• 5 years ago

Lancet seems to be a respected journal and it confirms those numbers.

ArgyleSound3• 5 years ago

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.

DivestTrump• 5 years ago

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.

temporalparts2• 5 years ago

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].

[0] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

[1] https://g.co/kgs/u6wvJ8

gus_massa2• 5 years ago

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.

dikei• 5 years ago

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.

major5055• 5 years ago

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.

coliveira4• 5 years ago

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.

IG_Semmelweiss• 5 years ago

article clearly states that other governments have raised similar concerns. Its not just brazil

in fact, article states brazil wasn't even the first

is_true3• 5 years ago

Argentinian government basically told it's own version of anvisa to approve the vaccine. That's it.

eliseumds• 5 years ago

The same organisation is putting pressure on Pfizer as well for lack of quality-control data: https://valor.globo.com/brasil/noticia/2021/04/26/impasse-co... (in Portuguese).

It looks like it shouldn't have been approved in the first place then.

cyclo64• 5 years ago

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.

SpaceRaccoon• 5 years ago

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.

[0] https://www.washingtonpost.com/world/2021/03/16/hhs-brazil-s...

irae• 5 years ago

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.

major5055• 5 years ago

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.

marcosdumay3• 5 years ago

It's not only that, but the manufacturer refusal to present all kinds of evidence was very public and undeniable.

coliveira4• 5 years ago

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.

b0sk• 5 years ago

Here's a follow-up post on the behavior by the Sputnik V Twitter account https://blogs.sciencemag.org/pipeline/archives/2021/04/28/ru...

Greg Lowe is a very respected commentator on all things vaccines.

js2• 5 years ago

Derek Lowe.

randomsquared3• 5 years ago

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.

is_true3• 5 years ago

Brazil is using the Chinese vaccine. Don't think they would if those claims were true

doliveira2• 5 years ago

Making sense in your head and fitting a narrative is not enough to make a claim correspond to reality.

chupasaurus• 5 years ago

The respone from Gamaleya: https://sputnikvaccine.com/newsroom/pressreleases/sputnik-v-...

major5055• 5 years ago

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.

marcosdumay3• 5 years ago

Thanks to mistakes and possible crimes commit by the Brazilian goverment, when rejecting other vacines

Well, that's the first COVID-19 vaccine the Brazilian government has rejected.

Clewza3132• 5 years ago

Which Derek Lowe tears to shreds in a followup:

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.

pixelkritzel• 5 years ago

Virologist Dr. Angela Rasmussen about the ability of the vector virus to replicate

https://mobile.twitter.com/angie_rasmussen/status/1387397186...

gnfargbl• 5 years ago

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?

ArgyleSound3• 5 years ago

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.

bildung• 5 years ago

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."

marcodiego2• 5 years ago

Covid19 has been extremely politicized in Brazil. President's supporters were mostly against vaccine until coronvac (sinovac vaccines) was approved by anvisa, Brazil's equivalent to FDA.

In Brazil this pandemic took ridiculous proportions. In the beginning, it was said that it wouldn't kill even 800 people[0]. It was said that it would be no more than a little flu and that children should not skip schools[1]. After thousands deaths, the president said, when asked about it, "So what?"[2].

Parallel to that, special secretary of culture, (which was once ministry of culture), was ousted[3]. She was replacing the previous secretary who (SERIOUSLY) emulated Goebbels on an official announcement[4]. On the education side, a "twitter-boy" with spelling difficulties[5] replaced the previous minister who was very weak technically[6]. It was then replaced by a liar[7] and then by an homophobic[8].

Some states then started restrictive measures to control the spread of the virus. The president was against it, the supreme court had to intervene to guarantee that states could apply restrictive measures[9]. A false narrative started trying to blame problems during the pandemic on governors because the president "couldn't act". A false dichotomy also spread by supporters saying that restrictive measures hurt economy and that it could kill more people than the pandemic. It actually is the opposite, but it has grown among his supporters.

Then came choloquine, hidroxicloroquine, ivermectin, and nitazoxanide, not exactly in this order. The Chloroquine 'venture' was the most interesting. The president pressured the health minister to encourage it. As he refused, he was ousted[10]. The same pressure was tried on the next minister. He was ousted too[11].

Things got worse and his supporters began anti-democratic demonstrations asking for a pro-president coup[12]. Supreme court was attacked and people were arrested[13].

While the president discouraged the use of masks and social distancing, the number of daily deaths stayed on an elevated plateau[14]. Debauchery of sick and dead became common[15].

By the end of the second half of 2020, some vaccines were offered but refused[16][17]. The minister asked "why such a hurry?"[18] and the president said "The hurry is not justified"[19].

Things improved a little by the end of the year, people relaxed and met their relatives on year end's festivities. This had consequences and 2021 arrived. New variants surged and number of deaths started to rise again. In Manaus, hospitals run out of O2 and people suffocated to death[20]. Variants continued spreading and another health minister was replaced. Vaccines were approved and people began to be vaccinated.

By the end of April with around 14% of the population having at least one vaccine dose, numbers of daily deaths began to fall.

Some facts were not listed on the correct order, but today is April 28 and, according to worldometers.info, we're now at position 14 and soon there will be more deaths per million than in the UK. Brazil has the lowest median age population among nations with the most deaths.

No other country handled the pandemic worse than brazil.

[0] https://www.dw.com/en/opinion-bolsonaro-lets-100000-die-of-c...

[1] https://edition.cnn.com/2020/05/23/americas/brazil-coronavir...

[2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

[3] https://www1.folha.uol.com.br/internacional/en/culture/2020/...

[4] https://www.theguardian.com/world/2020/jan/17/brazil-culture...

[5] https://www.france24.com/en/20200110-brazil-s-education-mini...

[6] https://brazilian.report/power/2019/03/28/brazil-disastrous-...

[7] https://www.theguardian.com/world/2020/jul/01/brazil-educati...

[8] https://www.telesurenglish.net/news/brazil-education-ministe...

[9] https://www.aljazeera.com/news/2021/3/20/bolsonaro-asks-supr...

[10] https://brazilian.report/liveblog/coronavirus/2020/05/21/for...

[11] https://www.hindustantimes.com/world-news/bolsonaro-s-love-f...

[12] https://www.dw.com/en/brazilian-president-bolsonaro-sides-wi...

[13] https://brazilian.report/liveblog/coronavirus/2020/06/14/bra...

[14] https://www.theguardian.com/world/2020/jun/23/brazilian-judg...

[15] https://www.theguardian.com/world/2020/jul/08/bolsonaro-mask...

[16] https://theconversation.com/brazils-president-rejects-covid-...

[17] https://apnews.com/article/virus-outbreak-brazil-state-gover...

[18] https://www.nytimes.com/article/brazil-coronavirus-cases.htm...

[19] https://www.reuters.com/article/uk-health-coronavirus-brazil...

[20] https://www.caritas.org/2021/02/oxygenformanaus/

Clewza3132• 5 years ago

No other country handled the pandemic worse than brazil.

Yup, even Bloomberg agrees: Brazil is at the very bottom of the resilience rankings.

https://www.bloomberg.com/graphics/covid-resilience-ranking/

meepmorp6• 5 years ago

You make a good case, but you do have to admit that Narendra Modi is also a solid contender for shittiest handling of COVID. Just letting the Kumbh Mela go ahead this year earns him a spot near the top.

inglor_cz• 5 years ago

Live by ideology, die by ideology.

I am not trying to defend the Indian PM, whom I barely know by name, but it is not as if the West does not have similar weaknesses. Mass BLM rallies were allowed to go forward because the political price for banning them and enforcing the ban through use of force would have been too high. Even though it was already known that going to rallies is a risky behavior.

Fortunately for the U.S. at that moment, no extra infectious variant was in circulation. AFAIK India has a nasty variant that makes things worse.

19f191ty• 5 years ago

India is catching up

randomsquared3• 5 years ago

That is not mutually exclusive to investigators finding problems with Sputnik V.

marcodiego2• 5 years ago

And...?

rbanffy3• 5 years ago

It’s being said they didn’t actually test it.

exmadscientist• 5 years ago

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?

marcosdumay3• 5 years ago

Has there been any controlled study on the efficacy of Sputnik V? I haven't heard of any.

drewblaisdell• 5 years ago

You're asking if there has been any controlled study of Sputnik V, a vaccine which has been administered to millions?

sanxiyn4• 5 years ago

Yes there has been. https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

dragonwriter• 5 years ago

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.

Exmoor3• 5 years ago

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.

petertodd• 5 years ago

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.

cblconfederate• 5 years ago

More importantly is it possible to infect others with the vaccine?

Animats• 5 years ago

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.

throwaway4good• 5 years ago

I thought this NY times op piece on Russian and Chinese vaccines was interesting:

https://www.nytimes.com/2021/02/05/opinion/covid-vaccines-ch...

It’s Time to Trust China’s and Russia’s Vaccines

Basically non-western medical companies such as the Russian and Chinese vaccines companies have a much higher bar to reach in order to get their products approved.

Quality control issues and incomplete documentation are serious problems, but also fixable. Right now the world (maybe not us in the west) need Russian and Chinese vaccines as what the west can offer is not enough to go around.

weinzierl3• 5 years ago

I'm a complete layman but reading about the replication prevention I wonder:

Could it be that they left E1 intact deliberately? I suppose (naively) that a virus that replicates should cause a stronger immune system response and therefore increase efficacy. Being an adenovirus the worst thing that could happen is that you get a common cold.

Common cold once vs potential death is not the worst trade-off imaginable, if you ask me.

sanxiyn4• 5 years ago

Gamaleya themselves says they removed E1. There is no reason to doubt it.

weinzierl3• 5 years ago

Thanks, that makes sense.

fsh• 5 years ago

This is addressed in the article:

Now, there have been debates over the years about whether you’d get a more effective vaccine that way, with a “replication-competent” adenovirus, but generally it’s believed that you can do fine with the “replication-incompetent” ones, which let you *not* give your patients a new viral infection at the same time.

weinzierl3• 5 years ago

Thanks, that takes away the premise of my question.

d1sxeyes• 5 years ago

Also, would this be transmissible? Could vaccinated person A infect unvaccinated person B, leading to community transmission of immunity?

I'm not an expert in this field, but it sounds logical at least, and provides a motive for the discrepancy.

zgcarvalho• 5 years ago

I would like to add information that I believe is very relevant.

During the pandemic, the congress approved a law (Article 16, Law No. 14.124/2021)[1] that defines a limit period of 30 days for Anvisa to approve or disapprove the vaccine. If, after 30 days, Anvisa does not issue its final recommendation, the vaccine is automatically approved. I think this law is absurdly stupid, but let's get back to the facts.

Days before denying Sputinik's authorization to use, Anvisa asked the Federal Supreme Court (STF) to suspend the 30-day period alleging that the data received were incomplete and information was missing.

A supreme court judge denied, on March 26th, the suspension of the deadline saying that this possibility was not manifested in the law. And he added that Anvisa's decision must be technically based, "not admitting the mere allegation of insufficient documentation or the simple allusion to potential risks". And if Anvisa does not decide on import and distribution authorization requests within 30 days, the interested parts are automatically authorized to import and distribute Sputnik V [2].

One day after the judge denied the suspension of the term and one day before the deadline, Anvisa denied the request.

[1] https://www.in.gov.br/en/web/dou/-/lei-n-14.124-de-10-de-mar... [pt]

[2] https://agenciabrasil.ebc.com.br/saude/noticia/2021-04/lewan... [pt]

meepmorp6• 5 years ago

The automatic approval law is incredibly stupid. Your timeout mode shouldn’t be to automatically approve medicines when the regulator takes over a month to issue a decision.

Thanks for the context, this is probably a large part of the decision. Not enough time for due diligence, and the only option to prevent automatic release of a potentially problematic medicine is outright rejection.

Brazil Rejects the Gamaleya Vaccine

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