June 19, 2020

Weekly line: Llamas, alpacas, and cows? They're all key to combating Covid-19.

Daily Briefing

    As the global coronavirus pandemic continues to worsen in the United States and many other countries, researchers worldwide are scrambling to develop a vaccine against the virus and treatments for Covid-19—and some are betting on llamas, alpacas, and cows to get us there.

    What we can (and can't) expect from a coronavirus vaccine

    Alpacas, llamas, cows—and their antibodies (oh my)

    Alpacas, llamas, and cows have long been important to medical researchers, particularly because of their antibodies, which could be used to help fight infectious diseases.

    In alpacas and llamas, researchers have discovered nanobodies, which are much smaller than the full-size antibodies that humans produce. And because nanobodies' smaller size make them easier to manipulate than larger antibodies, scientists can more readily edit them to potentially protect against or attack some viruses. These nanobodies also are more stable than larger antibodies—and "faster and cheaper to make than their larger counterparts," Science Magazine's Mtich Leslie notes.

    Further, research has shown that antibodies found in llamas can neutralize some viruses. Over the past 10 years, scientists have launched projects evaluating whether llama's antibodies could be used to combat infectious diseases such as HIV, influenza, SARS, and MERS—and have found promising results.

    Researchers also have recruited cows into efforts to fight influenza and MERS, though scientists focus on a different type of antibody—called polyclonal antibodies—in those animals. Polyclonal antibodies include a mixture of heterogeneous molecules that are secreted by several different immune cells to target a particular pathogen. The molecules can interact with different epitopes—which are the parts of a virus molecule to which antibodies attach themselves—on the same pathogen. That differentiates them from monoclonal antibodies, which are a group of homogenous molecules produced by one clone of plasma B cells to target a particular pathogen. Monoclonal antibodies can interact with just one specific epitope on a pathogen.

    Like the antibodies found in llamas, research has shown that polyclonal antibodies produced in cows can neutralize certain viruses.

    How researchers are using alpacas, llamas, and cows in efforts to fight the new coronavirus

    So what does all that mean for efforts to fight the new coronavirus? It depends on the animal.

    In alpacas, researchers are looking to harvest and edit monoclonal nanobodies from the animals to attack the new coronavirus.

    For one project, researchers at the Karolinska Institute in Sweden have injected a 12-year-old alpaca named Tyson with proteins of the new coronavirus and have harvested and cloned nanobodies from his blood that adhere to the same epitope of the virus as human antibodies. The researchers next will test those antibodies in other animals, such as mice and hamsters, to determine whether Tyson's antibodies can neutralize the new coronavirus—meaning they could block or treat the virus—in other species.

    If successful, it's possible researchers could use the nanobodies to create a treatment for Covid-19, the disease caused by the virus. For such a treatment, providers likely would inject patients who test positive for the new coronavirus and whose immune systems are struggling to fight the infection on their own with the nanobodies, which could help bolster the patients' attack against the antigen.

    In a separate project, researchers are examining whether they can use similar antibodies from llamas to create therapies for Covid-19. In a study published last month in the journal Cell, researchers noted that nanobodies harvested from a llama named Winter—whose antibodies already have proven effective against the coronaviruses that cause MERS and SARS—showed promise of neutralizing the new coronavirus after she, too, was injected with proteins from the virus. The researchers are hoping those miniature antibodies could attack the novel coronavirus by "sneak[ing] into spaces on viral proteins that are too tiny for human antibodies," The Guardian's Matthew Cantor writes.

    Ultimately, the researchers hope they'll be able to use Winter's nanobodies to create treatments for Covid-19—as well as a prophylactic against the new coronavirus that would be injected into people who haven't yet contracted it. However, the researchers noted that the nanobody prophylactic likely wouldn't provide patients with long-term protection against the virus, like we see with vaccines against the measles (which provide permanent protection) or with influenza vaccines (which provide protection for several months). Instead, a nanobody vaccine against the new coronavirus likely would provide patients with protection only for a month or two before they'd need to receive the prophylactic again, the researchers said. As Salon's Nicole Karlis explains, that's because the nanobody prophylactic would provide patients with "immediate protection" against the new coronavirus, as patients would receive "the antibodies directly," but it wouldn't cause patients to create their own, new antibodies against the virus, as typically occurs with vaccines that provide long-term protection.

    When it comes to cows, researchers are taking a different approach. NPR's Joe Palca reports that scientists at SAB Biotherapeutics in the past have created polyclonal antibodies in cows that were effective at neutralizing influenza viruses and the coronavirus that causes MERS—and now are working to see whether the antibodies could be used against the novel coronavirus.

    According to Palca, these cows are "special," because they've "been given genes from the human immune system that make antibodies." Researchers have injected the special cows "with what essentially amounts to a coronavirus vaccine," Palca writes. And according to SAB CEO Eddie Sullivan, the researchers are now monitoring the animals to see whether they "produce a specifically targeted high-neutralizing antibody that can be used in patients."

    Palca explains that those antibodies potentially could be used like a vaccine, to help prevent someone from contracting the new coronavirus if they're exposed to it, or as a treatment to help slow the virus' progression—which, in turn, might slow the progression of Covid-19.

    When could we see treatments or a vaccine derived from these animals' antibodies?

    While researchers are optimistic about the possibility of creating a treatment for Covid-19 or a vaccine against the new coronavirus from the antibodies harvested from alpacas, llamas, and cows, it's worth noting that it could be at least several months before any of the therapies could be authorized for use in humans—and there still are many benchmarks researchers would have to meet to get there. All three research projects mentioned above are in their early stages and would need to advance to go through clinical trials showing that any therapies derived from the antibodies are effective and safe in humans.

    But, if they move past those thresholds and help to thwart the global coronavirus pandemic, it might be time we start paying our respect to alpacas, llamas, and cows in new ways—at least according to one researcher. Xavier Saelens—a molecular virologist at Ghent University in Belgium who is working on the project using Winter's antibodies—told the New York Times' Jillian Kramer, "If it works, llama Winter deserves a statue."

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