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    The vaccines and the variants: Four keys to ending the pandemic

    Vaccines work well against the current variants, but to end the pandemic, we need to stay ahead of the evolving virus.

    Three differently colored virus particles depicted as racing each other

    Editor's note: An additional variant of concern, omicron, was identified in South Africa in November 2021. This article does not contain updated information about this highly transmissible variant, which quickly became the dominant strain circulating in the United States in December 2021. 

    After more than a year of recommending strict precautions to curtail the spread of COVID-19, the Centers for Disease Control and Prevention (CDC) recently gave the green light for the country to creep back toward a sense of pre-pandemic normalcy.

    On May 13, the agency said that fully vaccinated individuals no longer need to mask or social distance in most situations, citing a growing body of evidence that the currently approved vaccines are extremely effective at protecting the recipient from both becoming sick and transmitting the virus to others.

    But the fact remains that, while fully vaccinated people can breathe a sigh of relief that they are well protected, the pandemic is far from over.

    Globally, the vast majority of people remain unvaccinated, and coronavirus variants continue to emerge. It’s also possible that vaccinated people will need to come back for additional shots as the virus evolves and immunity wanes. Some scientists are even developing a vaccine that would work against all variants, present and future.

    As the scientific world continues to study and fight the evolving virus, here are four keys to bringing the pandemic to an end.

    Vaccines must continue to combat variants

    “So far, we’ve been extraordinarily lucky that all the variants that have been identified are matched by the vaccines,” says Gigi Gronvall, PhD, an immunologist and senior scholar at the Johns Hopkins Center for Health Security in Baltimore.

    Scientists were in awe when the initial clinical trial results from the mRNA vaccines made by Pfizer and Moderna showed that they were more than 90% effective against symptomatic disease caused by the original SARS-CoV-2 strain. Since then, both laboratory and real-world studies have shown that the three vaccines approved in the United States continue to perform well, including against the currently known variants.

    These variants include:

    Alpha: First identified in the United Kingdom, this variant is believed to be 50% more transmissible than the original virus, according to the CDC, and now accounts for more than 69% of coronavirus infections in the United States. One real-world study in Qatar found that the Pfizer vaccine was 90% effective against symptomatic disease and 100% effective against severe disease.

    Beta: This variant, which was first found in South Africa, is one of the more concerning ones, as it is also 50% more transmissible than the original virus and seems to make the vaccines somewhat less effective. The Qatar study found that the Pfizer vaccine was 75% effective against symptomatic disease but still 100% effective against severe disease. Johnson & Johnson’s one-shot vaccine was 52% effective against symptomatic disease and 73%-82% effective against severe disease in its studies in South Africa, where this variant was dominant. So far, it accounts for less than 1% of infections in the United States, according to the CDC COVID Data Tracker.

    Gamma: This variant, originally identified in Brazil, has similar mutations to the beta variant, but there is less available data on its impact on vaccine effectiveness. It currently accounts for about 8% of infections in the United States.

    Delta: Scientists are still learning about this variant, which has raised international alarm after being detected during India’s ongoing COVID-19 crisis. One recent study in England — where the variant is spreading — found that the Pfizer vaccine works well against this variant, with 88% effectiveness after both doses. This variant appears to be as much as 50% more transmissible than the alpha variant, has quickly become the dominant one in the United Kingdom, and now accounts for more than 6% of cases in the United States.

    Epsilon: This variant is about 20% more transmissible than the original strain and likely drove a COVID-19 surge in California last winter. However, the alpha variant has taken over as the predominant one on the West Coast in recent months. There is little clinical data about this epsilon variant, but lab studies found that the current vaccines are likely to be effective against it.

    We must vaccinate the world

    The United States, which has fully vaccinated about half of its adult population, has seen a drop in COVID-19 cases since mid-April.

    But worldwide, just over 10% of the population had received one shot as of May 30, with high- and upper-middle-income countries accounting for 85% of all shots administered.

    “It’s a very different situation in the U.S. compared to the rest of the world,” says Peter Hotez, MD, PhD, co-director of the Texas Children’s Hospital Center for Vaccine Development and a professor in the Departments of Pediatrics and Molecular Virology and Microbiology at Baylor College of Medicine in Houston. “We’re kind of in this race to vaccinate as many people as possible.”

    With the new variants, those who are unvaccinated — and even those who are vaccinated but have compromised immune systems — remain vulnerable to COVID-19.

    One study published in JAMA that measured post-vaccination antibody production in organ transplant patients found that nearly half of the patients did not create antibodies and that those who were on immunosuppressant treatments were least likely to do so. Another preprint study looking at antibody response in patients with blood cancers had similar results.

    “We’re kind of in this race to vaccinate as many people as possible.”

    Peter Hotez, MD, PhD
    Professor at Baylor College of Medicine

    Immunocompromised people who develop COVID-19 could also have the additional risk of providing the coronavirus with a chance to mutate further. In a Nature article from earlier this year, physicians documented a case where the virus evolved during a prolonged infection of an immunocompromised patient.

    “The more transmission, the more opportunity you have for variants to evolve,” says Steven Zeichner, MD, PhD, an infectious disease expert and pediatrics professor at the University of Virginia (UVA) School of Medicine in Charlottesville. “From a U.S. perspective, getting everyone around the world vaccinated is not an altruistic thing. It protects us here in the U.S. The side effect is that it helps everyone else in the world.”

    We must ramp up genomic surveillance to keep up with new variants

    Another key to ending the pandemic relies on keeping up with evolving variants through genomic sequencing: a method that researchers use to analyze genetic mutations of the virus and understand what impact they might have on the pandemic, such as increased transmissibility or ability to evade antibodies.

    Labs across the United States have analyzed less than 2% of the total COVID-19 cases in the country — lagging behind more than 20 other countries, according to the online genome repository GISAID. By comparison, the United Kingdom has sequenced nearly 9% of its cases.

    However, efforts to sequence the virus have ramped up in recent months with help from the federal government, which partnered with public health and academic labs to collect, analyze, and publish sequencing data. In the first week of January, less than 3,500 sequences were published in the United States. That number climbed to more than 26,000 in the last week of May, according to CDC data.

    But according to a dozen researchers who spoke to Nature for an article published in April, the efforts to expand sequencing have been stunted by slow funding and coordination hurdles.

    “I think we’re underachieving,” Hotez says.

    A pancoronavirus vaccine could tackle all the variants — present and future

    Many scientists have hypothesized that vaccinated people will need to get additional booster shots as time goes on, but it’s unclear when that will be necessary. Pfizer and Moderna — the companies that manufacture the most commonly used vaccines in the United States — have released study results showing that their vaccines remain highly effective six months after vaccination. Some scientists believe that immunity could last for years, even after antibody counts recede, because of immune cells in bone marrow that can remember the virus long term. Even so, vaccine manufacturers are working on updated vaccine boosters to target the emerging variants should they be needed.

    And some researchers are working on even more ambitious vaccines that, instead of having to be tweaked to combat variants, would work against all coronaviruses and may even prevent the next pandemic.

    “We’ve looked at the history of coronavirus outbreaks: In 2003, there was a SARS-CoV-1 outbreak; in 2012, there was a MERS outbreak; and in 2019, we saw SARS-CoV-2,” says Kevin Saunders, PhD, director of research at the Human Vaccine Institute in the Department of Medicine at Duke University School of Medicine in Durham, North Carolina. “We anticipate there will be another coronavirus outbreak.”

    Early in the pandemic, Saunders and his team decided to repurpose several years of work on a vaccine for HIV to create a shot that would work as a booster for the COVID-19 vaccines. But as they worked, they realized that the nanoparticles they were programming with a particular part of the SARS-CoV-2 spike protein that is used to bind to human cells were effective against other coronaviruses as well.

    The Duke lab tested its vaccine in macaque primates and mice and found it to be extremely effective against several different coronaviruses, including the SARS-CoV-2 variants of concern and some bat coronaviruses that have the potential to fuel the next pandemic.

    “The advantage of our vaccine is it’s not just antibodies for one or more variant; it targets a spot on the spike protein that binds to the receptor,” says Barton Haynes, MD, director of Duke's Human Vaccine Institute and an author of the vaccine study. “What we’re working on now is to get it produced as quickly as possible under good manufacturing practice conditions and make sure it’s safe for testing in humans.”

    “We’ve looked at the history of coronavirus outbreaks: In 2003, there was a SARS-CoV-1 outbreak; in 2012, there was a MERS outbreak; and in 2019, we saw SARS-CoV-2. … We anticipate there will be another coronavirus outbreak.”

    Kevin Saunders, PhD
    Director of research at the Duke Human Vaccine Institute

    Researchers at the UVA School of Medicine and the Virginia-Maryland College of Veterinary Medicine at Virginia Tech have also developed a vaccine designed to work against a variety of coronaviruses, including SARS-CoV-2 variants. They employed a modernized version of a 100-year-old vaccine technology: using killed whole bacteria that have been reengineered to put a small piece of the virus on their surfaces. The scientists synthesized DNA that directs the production of the fusion peptide, which is a part of the spike protein that is common to all coronaviruses. They then inserted the DNA into a plasmid that instructs the bacteria to place the vaccine antigen on their surfaces, where it can be detected by the immune system.

    “One of our main motivations was getting down to a dollar a dose,” says Zeichner, who led the initiative at UVA. “The factories that make these killed whole cell vaccines already exist around the world, so modifying the procedures to produce a new coronavirus vaccine using our platform should be relatively straightforward.”

    Zeichner and his colleagues used the technology to test vaccines in pigs, targeting either SARS-CoV-2 or a distantly related pig coronavirus. They found that the vaccines were equally effective for both strains, which suggests they can be used to combat many variants and could be an approach to a universal coronavirus vaccine.

    These efforts might be just the beginning of a shift in vaccine development to targeting multiple strains of a virus at once.

    “There are a lot of really bad things about this virus — but one good thing is it is imminently vaccinatable broadly,” says Scripps Research Translational Institute Founder Eric Topol, MD, who co-wrote an article for Nature calling for greater investment into research for panvirus vaccines. “We could knock this out.”