The COVID-19 pandemic has lasted longer and had a far greater impact than many of us could have ever imagined. Did you really think you’d be vaccinated and still wearing a mask approaching 2022? In yesterday’s plenary session, “COVID-19: Vaccines and the Tango of Viral Evolution and Host Immune Responses,” Margaret Liu, MD, a leader in the science of vaccines and a global health expert, likened the evolution of the SARS-CoV-2 virus and our efforts to combat the virus to a tango dance, a series of fast, unpredictable, and tightly connected dance steps where we, the follower, must react quickly to the leader. Liu emphasized that we, as a global community, can’t stop dancing: We must evolve from follower to leader of this dance if we hope to breathe freely.

As an expert in the fight against the COVID-19 pandemic, Liu, CEO of PAX Therapeutics and Chairman of the Board of the International Society for Vaccines, stressed the importance of global vaccination and the need to remain vigilant with safety measures. While many countries have done well developing vaccine-based immunity, Liu, reminded the audience, “we are a global community, and no one is safe until we are all safe,” underscoring the fact that for our own self-interest—for humanity—we need to ensure we have a robust and effective global response. Liu described an unconcerted effort more like a game of whack-a-mole, where we react to emerging variants and hotspots, but we won’t ever have lasting success.

Liu eloquently explained that SARS-CoV-2 variants, like the Delta variant, have emerged due to an error-prone replication. This introduces amino acids changes in the viral protein that might change the properties of the virus. In the case of the Delta variant, mutations in the virus provided it with some selective advantages, such as higher infectivity and increased viral loads in asymptomatic individuals, enabling it to become the dominant variant. More variants are poised to arise if we don’t take action. “We need to control the development of mutants,” Liu said, and the best way to do so is to reduce the amount of virus out in circulation so there will be “fewer opportunities for new variants” to emerge.

Liu used data to debunk several misconceptions about our current vaccines that continue to circulate. The current vaccines available in the US and Canada have proven to be exceptionally safe. Of ~ 400 million administered doses there have been 5 deaths attributed to SARS-CoV-2 vaccines in contrast to the 685,000 COVID-19 related deaths. Those that are unvaccinated are five times more likely to be infected, and greater than 10 times more likely to be hospitalized or die from the virus, according to Liu.

While the news media often fixates on antibody responses to vaccines and the fact that antibody titers have been shown to decline over time, Liu noted that vaccines also activate T-cell responses against the virus. T-cell helpers produce cytokines that are the “vitamins of the immune response” and help stimulate antibody production and support another type of T-cell, the cytotoxic T-cells. “Cytotoxic T-cells shutdown infected cells that are the virus producing factories,” Liu explained. The current “gene-based” SARS-CoV-2 vaccines used in the US and Canada are particularly effective at generating these types of T-cell responses. This partly explains why vaccinated individuals may get infected but not seriously ill from the virus, as a functional immune system will elicit T-cells memory responses that quickly ramp up a pre-programmed immune response. Despite the effectiveness of vaccines, Liu highlighted several studies that indicate that boosters can prevent severe illness and therefore are recommended for certain individuals.

Liu had many answers, but there are questions that remain unanswered. It’s still not known if there is a specific amount of circulating antibody required for protection, and it remains unclear if there will be the need for variant-specific vaccines in the future, or when this tango will end. But it was very apparent we all are going to have to continue to dance until the music stops.