How challenging is it to update different types of vaccines?
How challenging is it to update different types of vaccines?
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SciLine tracks common science questions that reporters have about the coronavirus pandemic – and reaches out to our network of scientific experts for quotable comments in response. Reporters can use the comments below in news stories, with attribution to the scientist who made them.
SciLine tracks common science questions that reporters have about the coronavirus pandemic – and reaches out to our network of scientific experts for quotable comments in response. Reporters can use the comments below in news stories, with attribution to the scientist who made them.
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Expert Comments:
Dave O’Connor, PhD
It depends on the type of vaccine. One of the tantalizing features of the mRNA vaccines produced by Pfizer/BioNTech and Moderna is that making new vaccines with updated viral genetic coding should be very quick. I think that this technical simplicity could lull us into a false sense of complacency if we don’t also consider the underlying biology. What do I mean? When viral variants emerge in response to attacks from infected persons’ immune systems, that evolutionary pressure results in viruses that often are less effectively recognized by the immune system. For example, the B.1.351 variant (the “South African” variant) has a specific change called E484K in the spike gene. The ‘E’ here means that the original form of the virus encodes a glutamic acid amino acid residue in the 484th amino acid position of the virus spike protein, while the new B.1.351 variant viruses have a lysine amino acid (“K”) in this position. This change appears to reduce the ability of antibodies to recognize the spike protein.
If a vaccine is updated to encode the lysine—so that the vaccine spike protein matches the new variant spike protein—there is no guarantee that the new vaccine will elicit antibodies that are as potent as those elicited against the original virus’s spike protein containing glutamic acid. Moreover, antibodies directed against variant viruses with lysine at this site in their spike protein may continue to exert selective pressure which will lead to the emergence of another variant that is even more poorly recognized by antibodies. There is already anecdotal data* that the spike protein lysine found in the ‘South African’ B.1.351 variant can be replaced by another amino acid, alanine, that might be even harder for antibodies to recognize. So even if it is relatively easy to update the vaccines themselves, this doesn’t necessarily mean the updated vaccines will work as well.
Taking a page out of the book on HIV, where the emergence of variants has bedeviled drug treatment for decades, the ‘right’ answer is to reduce the amount of virus replication globally to give the virus fewer opportunities to spawn new variants. Reducing the ‘global viral load’ is critically important. If we give the SARS-CoV-2 virus huge numbers of opportunities to evolve variants that are adapted to replicate in the face of immune responses, it will.
Jiang Zhu, PhD
The time and effort required for updating a vaccine is determined by the underlying vaccine platform. In principle, it is easier to update nucleic acid vaccines, such as DNA, RNA, and viral vector-based vaccines, because scientists only need to incorporate the genetic information into these platforms. For protein-based vaccines, spike mutations can be readily made and tested, but it may take more time if a new family of cells that produce the spike protein for the vaccine has to be created and the manufacturing process has to be re-evaluated.
