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« In re Fulton (Fed. Cir. 2020) | Main | PTAB Grants CVC Motion for Marraffini Deposition »

January 26, 2021

Comments

This article seems to imply that the target mRNA is exogenously translated into protein, and that resulting protein is what is injected as the vaccine antigen. However, mRNA vaccines work by injecting the mRNA itself as the antigen. Then the injected mRNA is then translated by the host's immune cells to create the protein antigen in vivo, which results in the immune response.

The article seems to suggest that this is a problem peculiar to mRNA vaccines, and yet we know that this is not so. A killed virus vaccine will only have the antigens of the virus population from which it is taken - so new variants are no more addressed by a killed virus vaccine than by an mRNA vaccine. Would a vaccine be better with more than one antigen? - seems reasonable, but doesn't work for the flu vaccine.

Derek: Flu is a special case, for at least two reasons. One I allude to in the post: the frequent passage of the virus through animals (swine flu, for example), as opposed to viruses like SARS-CoV-2, which is a "jump" from the species it is adapted to (and in which it is not particularly lethal) to man. The other reason is that because the influenza virus genome is segmented so there is the possibility for reassortment of the viral segments to provide another level of variability.

The problem with mRNA vaccines is that when the mRNA is synthesized every molecule encodes exactly the same protein, which does not occur in a population of viruses any more than it occurs in a human population. I'm not saying the vaccine is not remarkable for how quickly it was developed and how effective is has been. But it is a good thing to recognize its limitations.

Thanks for the comment

Greg: sorry you got that impression; I thought it was evident that an mRNA virus was made in immune cells.

But the point is that the mRNA encodes one protein that is invariant in then encoded amino acid sequence. Thus, naturally occurring variants can arise that lack the immunological effectiveness that the vaccine has against SARS-Cov-2 virus having the same Spike protein from which the vaccine was made.

Thanks for the comment.

Nice article Kevin. One point worth mentioning is that the antibodies produced by the body upon injection of the mRNA and the resultant expression of the protein are polyclonal in nature and bind to different regions of the spike protein. So even if the virus mutates the protein, presumably we would have antibodies that might be effective against the mutated virus. So in order for the virus to mutate in a way to avoid the antibodies it has to find the right mutation that avoids antibodies but still retains the ability to bind to the receptor. While natural selection is pretty good at doing that, it's still a needle in a haystack. What do you think?

Dear Ken:

Agreed, the protein mutates at random and so it becomes combinatorial pretty quickly. But because RNA viruses lack access to most of the sequence correction mechanisms in the cell that DNA viruses benefit from there is a lot of variant production (one reason there is no HIV vaccine for example). And then we get to the economies of scale: estimates of there being 10 to the 23rd power (more than here are stars in the universe; https://www.airspacemag.com/daily-planet/there-are-more-viruses-earth-there-are-stars-universe-180974433/) viruses worldwide, and all you need it one to infect someone and start spread of the resistant variant. What makes viruses so successful.

Hope you are well.

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