As I understand, this kind of vaccine is a virus that can infect the cell, start synthesis of proteins encoded by its genome, but cannot finish the replication cycle till the proper end. It can have extra genes in its genome, encoding proteins that cause the wanted immunity to develop. Some important vaccines against COVID-19 are based on this approach.

The question is, how such an "incomplete virus" could be produced in large amounts? It would be logical to assume that it was replicating during the manufacturing process, but then why does it cannot any longer? The only hint I found is the usage of the "helper virus" that infects the same cell, so the "incomplete virus" can borrow some parts from the healthy "coworker". However this raises another question: the helper virus obviously replicates also itself, and how to discard it later without inactivating the "non replicating" one? It would just cause infection without any use if not discarded.

I have done some search over web and article databases but was not able to find a short and clear explanation of this method. The main focus of the works I found is always somewhere else. I understand that exact technology may be secret, but it is likely at least remotely based on some research work anyway.

How is a "non replicating vector" replicated to produce enough of it, for making a vaccine out of it?


Complementing cell line (or complementary cell line) is a cell line which has been genetically modified to produce proteins necesary for non-replicating virus replication. It is designed to express exactly the genes which had been deleted from virus to render it non-replicating. The non-replicating viral vector can replicate only in complementing cell line and not in other cells.

  • $\begingroup$ I have learned this in a lecture. I have tried to find some comprehensive reference for this answer but found only use cases. $\endgroup$ – BagiM Aug 18 '20 at 6:17
  • $\begingroup$ do you have any other good sources for "complementing cells lines? I upvoted your answer. By the way, does a Adenovirus vector for covid-19 vaccine carry the spike protein - as an experienced user would you think that's a good question to publish? How can Adenovirus be replicated in vitro without "expression" of the implanted mRNA for the spke protein? It should carry it. $\endgroup$ – Peter Bernhard Dec 13 '20 at 11:48
  • $\begingroup$ @Peter Bernhard Sorry only sources would be what I would google. I wouldn't call myself experienced user and I try to stay out of judging questions. You can ask the question but be careful to not conflate expression of protein with virion packaging. The host cell expresses and contains a lot of different proteins. Only specific proteins assemble into 3D structure to form a virion. $\endgroup$ – BagiM Dec 14 '20 at 13:20
  • $\begingroup$ Thank you. Good yo said "expression of protein", now up above "expression of genes" seems better in formulation. However, this improves ma understanding - the "cell line" as a helper adds the proteins, not the genes (correct me if I am wrong, please) that are necessary for a virus to still be an intact virus, for the purposes of vaccination, to be specific. So, "packaging" seems to be very illuminating: maybe packaging genes have been deleted, and the helper cell lines add that stuff, to build viruses that last their life time only. $\endgroup$ – Peter Bernhard Dec 16 '20 at 5:42

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