Producing adenovirus vector vaccines: Is viral replication an issue?


Jun 20, 2015
My intention is to discuss issues that come with mass manufacturing and the risks if there is a lack of effective quality control.

There are already several threads that discuss shedding and leaky vaccines. I put links below. Please don't derail this thread with case reports.


Earlier in April Slovakia claimed that the batches of Sputnik V vaccines it had received differed from those reviewed by international scientists and by the European Union regulator, and that it didn't match the description in the Lancet. Now it's Brazil who rejects the Russian vaccine saying that the cells that are used to make the adenoviruses for the vaccine development allow their replication. Russia rejects those claims. They say that the stuff goes through a four-stage cleaning and filtration process, something which makes their product more expensive but very pure.

This article discusses the mechanism of the potential replication issue:

Brazil Rejects the Gamaleya Vaccine

The adenovirus vector vaccines (all of them so far in the pandemic – AZ/Oxford, J&J, Gamaleya, CanSino) are made by removing most of the adenovirus DNA instructions from some form of the virus, and inserting DNA to make coronavirus antigens instead. Oxford has a chimpanzee adenovirus, J&J has been using the Ad26 strain, CanSino has the Ad5 adenovirus, and the Gamaleya vaccine is one shot of Ad26 followed by a shot of Ad5. But all of them carry the DNA to make the coronavirus Spike protein (some of them in its native state, others with stabilizing amino acid mutations). And all of them have had key parts of their original genome removed to make them unable to replicate in the body (deleting a gene called E1 is the standard way to do this).

There are still places where this can go wrong. Double-stranded DNA breaks, which can happen more or less randomly, are generally repaired by processes called “homologous recombination” and “nonhomologous end joining”, and these can lead to mix-and-match behavior between DNA from different sources. This process can be deliberately harnessed for gene editing – that’s what the classic CRISPR enzyme Cas9 does – but it can also be a source of trouble in a system like this one. There is a chance that the occasional viral particle might be able to regain the DNA sequence for the E1 protein by picking it up from the human-cell background. If that goes right (well, wrong), then that will turn it back into a replicating virus, and that’s just what it will do in your cell culture tanks.

There are several links in the article. I have not checked if they indeed confirm the mechanism the author writes about, but assumed all the above is correct ...

They say that in the making of Gamaleya vaccine (Sputnik V) they do a lot of cleaning and filtering to rule out that live virus is in the end product. How about the other adenovirus vector vaccines? Do AstraZeneca and J&J also come with the potential risk that there is live adenovirus in the end product? Adenovirus that it genetically modified to carry the gene that makes the spike protein? Does it all boil down to quality control?

My concern is that not only the trials of the vaccines were too short to know anything about long-term effects, and there's enough reason to believe that the results have been massaged heavily (check Peter Doshi's articles), but there are more problems on the manufacturing side. There are excipients in the end product that where not present in the vaccines used in the trials. This is discussed in more details in the articles linked in this post.

To produce on scale new manufacturing processes must be developed and optimized, and this takes time. It's a new technology after all, and the production has been ramped up so fast on such a huge scale. Do experienced employees to design and run those production sites grow on trees? As we have seen with the case of Emergent (J&J and AstraZeneca contractor) there are companies contracted that are known to have quality issues.

There have been countless cases of tainted vaccines in the past. There were numerous outbreaks in vaccinated populations. In case of a Pfizer vaccine for cattle the offspring had a fatal bleeding disorder because the were bovine cell lines left in the vaccine (search for 'bovine neonatal pancytropenia' or 'BNP').

The following article goes a little deeper into the challenges the manufacturers face.

Why manufacturing Covid vaccines at scale is hard

Related threads:

15 MILLION doses of J&J’s one dose Covid vaccine halted after ingredient mix-up



Threads that are dedicated to the question if the vaccines are posing a threat to the unvaccinated:

Transmissible Viral Vaccines... how the shots are affecting those who haven't taken it. They may be designed to do exactly that
Covid Part 2: Deadly Dust?
Live Viral Vaccines Are Shed From People Who Have Been Vaccinated
Addressing Geert Vanden Bossche’s Claims
Vaccines cause more dangerous strains to evolve and shed (from vaccinated hosts)
Does a Moderna vaccinated person cause harm to a non vaccinated person?
MRNA contagious to the unvaccinated?
Any danger of being in contact with vaccinated people?