There are a number of organisms that have come up with some genuinely unique adaptations over the 4+ billion years that life has been a going concern on planet Earth, and several of those relate to how organisms fight off diseases. When it comes to immune systems, human beings are actually blessed with a robust and active system with a multitiered approach to fighting off parasites, bacteria, and viruses. As evidenced by what’s going on right outside everyone’s doors at the moment, that system is far from perfect, but compared to many organisms—including many other mammals—it’s remarkably effective.
Among the genuine oddballs in immune system developments are the camelids, a group that includes the familiar desert-crossing camel and its New World relatives: llamas, guanacos, alpacas, and vicunas. This whole group has an immune system that includes “single-domain antibodies,” also known as “nanobodies.” It’s been known for three decades that these nanobodies provide camelids with an extra layer of protection against viruses, but for an equally long period, advances in using these compounds in pharmaceuticals have been tied up in a series of intellectual property rights disputes. However, it seems that something on the scale of a global pandemic may have shaken loose this new immunity arrow—and allowed scientists to develop a powder people could inhale that fights COVID-19.
A paper published by the National Institutes of Health (NIH) back in 2017 provides an overview of the nanobodies. Most antibodies, like those humans produce when exposed to COVID-19 or any other virus, contain four chains of molecules: two “heavy” chains and two “light.” That’s not true of camelids. They have antibodies that consist of only the heavy chains. These molecules are only about one fourth the size of normal antibodies.
In lab tests, these smaller nanobodies bound strongly to virus particles and camelids injected with “targets of interest” (i.e., scary viruses) produced nanobodies specific to those targets. There was concern about the potential for these molecules to produce a bad reaction in humans because heavy-chain disease is a real, if exceedingly rare, thing. That doesn’t seem to be the case. Everything appeared to be very promising. These molecules appear to more specifically and forcefully address viruses in part because they could literally fit into spaces in the complex geometry of virus surfaces and cell boundaries that the larger human-style antibodies can’t match. The potential is enormous.
Then came two decades of companies fighting about who has the right to bring the first camelid-based drug to market. The reason for this is that the potential really is enormous—these nanobodies could replace an existing market for antibodies that are used in treatment of everything from kidney disease to cancer, as well as opening up new markets, making them worth billions. As of 2018, several major treatments were hovering on the brink of release, subject to a lot of back and forth over claims about intellectual property. That included a potential cancer treatment described in Science Daily as a potential means of targeting and blocking the growth of cancer cells.
The potential for using nanobodies against COVID-19 was realized early on, and in May the NIH reported on University of Texas researchers who injected llamas with the SARS-CoV-2 virus. The llamas developed nanobodies specific to the critical “spike proteins” that the virus uses to enter human cells. That research is still ongoing and may result in a vaccine based around the generated nanobodies.
But on Tuesday, a preprint of a paper from a team from the University of California at San Francisco (USCF) announces that they have created a synthetic nanobody that can be turned into a fine powder, which can be used for “inhaled sprays to the nose or lungs.” Like the very much not tested homemade vaccine being shared around by MIT researchers, the UCSF inhaled treatment could be self-administered. Meaning that it might be possible to pick up an inhaler, take one or two shots over a period of a couple of weeks, and secure immunity to COVID-19. This has multiple advantages over coming into a doctor’s office or clinic for an injection, including reduced need for medical personnel to administer the vaccine, less exposure to other people in getting vaccinated, and potential distribution in areas where ordinary vaccines are hard to deliver.
Also, many of the side effects associated with COVID-19 vaccines in early trials were connected with the most simple fact about getting a shot: It’s a shot. People often complained about the pain and had associated ache and redness around the site.
A vaccine that is able to be inhaled to protect against COVID-19 is enormously appealing. However there are a couple of things to keep in mind:
- Like the memory RNA in the Moderna vaccine, this is a new technology potentially coming to market without a long history of human use to determine safety.
- Like the MIT homebrew, this is currently an untested product in humans. In fact, neither has been tested in any real sense. If someone offers you an anti-coronavirus snort at the moment, just say no.
- There’s another team from China that has also made a synthetic nanobody against SARS-CoV-2. They also don’t seem to have done any human (or animal) testing.
Barring the most extraordinary circumstances, odds are that when it comes time to get a vaccine against COVID-19 sometime early in 2021, it will be an injection based on one of the multiple large efforts now in phase three trials, not a powder created from synthetic camel nanobodies.
Still, it’s nice to think this event might have produced something useful, like moving along a technology that could genuinely produce useful treatments not just for COVID-19, but for a whole raft of diseases. And it’s coming to you … from llamas. Llamas. Llama. Llama. Llama.
I was going to resist the urge to say “meditate on that for awhile.” Except, of course, I didn’t.
Thanks to those who sent messages and links urging me to cover the llama news.