Will Our Current mRNA Vaccines Overcome Omicron?

Since the omicron variant was first identified in South Africa in late November, it has shown up in more than 20 countries, including the United States. Early reports suggest that this new coronavirus variant has more mutations than previous variants like Delta and thus may evade the immune response of vaccinated people more easily. On the positive side, a recent study of the Pfizer-BioNTech vaccine suggests that the vaccine still offers some measure of protection against the omicron variant and that booster shots could be key in limiting its spread. 

As colder weather and the upcoming holiday season bring more indoor gatherings, Columbia News wondered how well current mRNA vaccines will fare against this new foe. We spoke with two Columbia Engineering professors about updating the vaccines, the dangers of a partially vaccinated world, and why testing is so key.

Sam Sia is a professor of biomedical engineering who specializes in tools for rapid diagnosis. As the pandemic enters a new phase, Sia’s group is devising a new, at-home COVID-19 test that is both fast and highly accurate, combining state-of-the art molecular diagnostics with a streamlined platform to deliver results in less than ten minutes.

Jingyue Ju is a professor of chemical engineering and pharmacology who identified a library of molecules that target and inhibit a viral protein known as a polymerase that enables the coronavirus to replicate within infected human cells.

Q. There are promising signs that our current mRNA vaccines and boosters work against Omicron. How will we know when a new vaccine is needed? 

Sia: The current mRNA vaccines are based on injecting into the body a molecule—the mRNA—that holds the code for a viral protein. The body reads this message and produces copies of the viral protein. It then launches an immune response against these same viral protein copies. However, if the viral protein mutates, the antibodies and T cells trained to attack the original sequence may no longer neutralize the mutated virus. If that happens, and the new variant causes severe disease, then the vaccine needs to be updated to prime the immune system to fight this new invader.

Q. Experts have warned that a partially vaccinated population could increase the risk of new mutations. Given the high numbers of unvaccinated people globally is it inevitable that vaccine updates will be needed?

Sia: Each time the virus encounters a vaccinated individual, there’s a chance that a random mutant will evade the host response that was primed by a previously designed vaccine.

This dynamic is another reason that full vaccination is so critical. The more we accept the pandemic as a chronic condition, the more the virus hangs around vaccinated individuals and the greater the chance a new variant breaks through.

Ju: We can already produce a COVID-19 mRNA vaccine using a combination of RNA sequences that target several variants at once. If new variants prove to be more infectious or cause more severe illness, an update will be required. The nature of the coronavirus is advantageous in this regard. It has a relatively large RNA genome with a unique proofreading function to correct errors during viral RNA synthesis. This means it doesn’t mutate as frequently as influenza and HIV, which have no proofreading function.

Q. How long does it take to roll out a new mRNA vaccine? Are flu vaccines updated the same way?

Sia: mRNA vaccines are based on nucleic acids rather than proteins which makes it easy to change the sequence. It takes virtually no time to manufacture a new vaccine once a new coding sequence is identified. Flu shots, by contrast, are based on proteins and take time to manufacture. Flu vaccines need to be updated each year to match the strains that are circulating.   

Ju: An mRNA vaccine can be updated in a couple of weeks but it takes about three months to roll out to make sure that all regulatory requirements are met and that the vaccine is safe and effective.

Q. Will PCR and antigen tests for diagnosing COVID need to be updated? What about genomic tests that tell doctors which variant you caught?

Sia: So far, diagnostics tests have not required a change. PCR tests typically target the nucleocapsid proteins or other parts of the viral sequence that so far have not mutated very much. Antigen tests, on the other hand, may be more susceptible, because they use antibodies that target parts of the viral protein that may be more susceptible to variation. We will see if this becomes an issue for either the PCR or antigen tests for future variants. 

Ju: We need to be quicker about identifying new variants. Coronavirus genome sequencing, coupled with laboratory immuno-testing, is a good way to identify new variants; we just need to do more of it. 

Q. Is the United States testing enough compared to other countries?

Sia: Diagnostic-wise, we’re in good shape. Diagnostic PCR testing is now widespread in Western countries since enough labs have been able to expand their capacity. As diagnostic rapid antigen tests become more popular, we could see a supply chain crunch.

Ju: To keep up with emerging coronavirus variants, more genome sequencing in the U.S. is needed.

Mindy Farabee is associate director of editorial communications at Columbia Engineering.