A good thing about current vaccines is that they can be updated pretty quickly. So, if the virus evolves to evade vaccine-induced immunity, then I think we can definitely envision a situation like we have for influenza vaccines, in which the SARS-CoV-2 vaccine is periodically updated to keep pace with viral evolution. We do not yet know whether this will become necessary, but I think we are positioned to adapt quickly if it does.

All vaccines that have been deployed to date or are currently in development utilize the SARS-CoV-2 spike protein as the target of the human immune response. In the short to medium term, modification of the spike protein sequence in the vaccine to account for genetic changes in the virus should re-establish vaccine efficacy if it becomes significantly degraded.

These changes are easier to make for certain types of vaccine platforms, like the mRNA-based vaccines (Pfizer and Moderna), and more challenging for others, like the virus-vectored vaccines (AstraZeneca and Johnson & Johnson). Eventually, it would be desirable to develop vaccines that target regions of the SARS-CoV-2 spike where mutations would prevent the virus from functioning, such as the S2 region. Influenza A virus vaccines provide a useful analogy. Existing vaccines largely target portions of the influenza virus spikes that can mutate while the virus is still able to infect people, which is why the vaccine must be fine-tuned every flu season. Current efforts are aimed at targeting more genetically constrained parts of the flu spike protein—that is, parts that are so essential that any mutation would effectively disable the virus—to make ‘universal’ flu vaccines. In the medium term, it is probable that a strategy similar to the one currently used for flu will be necessary to protect the global population against SARS-CoV-2.

Fortunately, the vaccines that have been approved are types—mRNA vaccines or adenovirus-based vaccines—where the new, resistant SARS-CoV-2 spike protein gene sequence could be quickly swapped, and a new vaccine could be tested minimally and manufactured within a few months (unlike flu vaccines, which take much longer to prepare each year). It is also possible that other types of vaccines, such as live-attenuated (weakened virus) versions that include the full complement of the SARS-CoV-2 proteins and therefore more targets of immunity, could yield more durable immunity that is also less susceptible to new variants developing resistance. However, live-attenuated vaccines require much more thorough safety testing than the mRNA and adenovirus-vectored vaccines, which is why these were the first to be deployed, so they are still probably years away from potential licensure.