Annual Vaccines May Be Necessary: Lessons from the COVID-19 Genome

The genomic field continues to shed light on COVID-19. The latest: vaccination frequency, new therapy options, and unexpected mutations in the virus.

In the 14 months or so since the world was first alerted to the original SARS-CoV-2 outbreak, scientists have moved with remarkable alacrity to understand the virus, its effects on humans, its transmission patterns, and more. Last fall, we reported on the many advances that had come from the genomics field. This month, scientists at the virtual Advances in Genome Biology & Technology conference gave new updates showing the ongoing contributions of genomics as the world continues to battle the pandemic.

1. We Might Need Vaccines Every Year

Since the start of the pandemic, there’s been a lot of speculation about what kind of vaccine response would be needed. Would one vaccine provide a lifetime of protection? Or would we need frequently updated jabs, like we do for influenza? Trevor Bedford, an expert in infectious diseases and vaccines at the Fred Hutchinson Cancer Research Center, has been crunching the data to answer those questions. At first glance, annual updates would appear unnecessary: the SARS-CoV-2 virus seemed to mutate more slowly than most other viruses, and based on what we know about its coronavirus cousins, Bedford initially thought that updating the vaccine every four or five years seemed sufficient. But enormous volumes of new genome sequence data from all corners of the world have shown that some strains of the virus are accumulating mutations much faster than expected. Even more disturbing, many of those changes affect the spike protein, which is what current vaccines target to give us protection. Now, the virus’s mutation profile looks more like fast-changing influenza, Bedford said at the conference, suggesting that frequently updated vaccines — possibly as often as every year — may be necessary.

2. A Common Blood Pressure Med Could Help COVID-19 Patients

In order to thrive, the SARS-CoV-2 virus needs its host to have certain traits. For example, we already know that the spike protein it uses to invade our cells relies on a specific molecular dock — a receptor called ACE2 — found on some human cells. In New York, Neville Sanjana and his team wanted to know which other human genes are needed by the virus. They used CRISPR gene editing in cells to turn off all 20,000 human genes, one by one, and study how those cells responded when exposed to the SARS-CoV-2 virus. Next they drilled down on the hundreds of genes that were most important for infection, focusing on ones that can be inhibited by commercially available medications. While this exercise yielded several promising options, Sanjana highlighted amlodipine, an FDA-approved drug for high blood pressure that people have been taking safely for years. In lab studies, amlodipine successfully blocked SARS-CoV-2 infection, making it a potential treatment for people who do get COVID-19. It is an elegant example of how genomics enables a kind of rapid response to a disease outbreak that could never have been possible before.

3. More Contagious Variants May Be Survivors of Our Immune Systems

One of the first discoveries about the SARS-CoV-2 virus was its relatively stable genome. This frustrated scientists who couldn’t easily track transmission patterns because there were so few mutations, but it was great news for vaccine and therapy developers. Now, though, some of the emerging variants causing concern — such as the variants first identified in the UK, Brazil, and South Africa — have been found to harbor many more mutations than should be possible given viral evolution patterns. Worryingly, variants that emerged independently share some of the same mutations, a sign that these changes confer significant fitness advantage to the virus. Scientists are now working with the theory that these variants are evolving within individuals suffering from prolonged infection. The virus is working against the person’s immune response for an extended period. While the immune system will knock down weaker versions of the virus, any variant that acquires mutations that allow it to evade immune cells will be significantly stronger. Because of the prolonged infection, this process happens iteratively, creating versions of the virus that have accumulated many mutations. These variants can be less susceptible to immune response and more effective at infecting cells.

4. Genome Sequencing Ramps Up

Around the world, researchers are using DNA sequencers to map as many samples of the virus as possible. In countries like the U.S., those efforts are finally ramping up for the first time right now. In countries like the U.K., this has been a priority from the beginning. More than 600,000 SARS-CoV-2 genomes in total have been sequenced and shared with the global GISAID database so far. This January alone saw 125,000 genomes reported. In the U.K., scientists churning out these sequences are using the data to spot emerging variants, such as the more contagious B.1.1.7 variant that has now spread globally. By pairing genomic data with other information about the virus, these researchers have been able to show the effectiveness (or ineffectiveness) of certain mitigation measures, finding that only a severe lockdown was able to reduce transmission of this variant. Still, scientists point out that many countries have done little or no genome sequencing, creating some dangerous blind spots in our ability to track the pandemic. Even the U.S. may be harboring more variants that we have yet to identify given our relative lack of sequencing until recently.

5. The Fight May Be Changing

Alongside the hope that vaccination programs will bring an end to the pandemic are concerns that the rules of engagement in this battle may be changing. “Now we’re in a different phase of the epidemic,” conference attendees were told by Eddie Holmes, the veteran virologist at the University of Sydney who shared the first SARS-CoV-2 genome sequence with the world. Selective pressures on the virus will change as more people are vaccinated and so many others have some protection from their own infections. That could bring the virus to heel, or it could force it to evolve into a more wily foe. Genomics will continue to be important in tracking SARS-CoV-2, but Holmes is already calling for increased surveillance of potential new outbreaks of viruses we’ve never seen before. Active, ongoing monitoring of people who interact with animals — in places like live animal markets or abattoirs, which Holmes calls the “fault lines” of viral emergence — would be an important step for detecting potential pandemic events when they’re still small enough to snuff out.

Sadly, the upshot of these and other genomic studies is that SARS-CoV-2 is likely on its way to becoming an endemic virus that we will never fully quash. Much like the flu, we may be dealing with this virus long after the worst of the pandemic is over.

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