Hiking is one of Marci Flory's favorite activities, but her chronic Lyme disease sometimes renders her unable to walk. Biotech companies Pfizer and Valneva are testing a vaccine for Lyme disease in a Phase III clinical trial.
“Initially doctors thought I had ALS, or less likely, multiple sclerosis,” she says. “But after repeated MRI scans for a year, they concluded I had a rare neurological condition called acute transverse myelitis.”
But Flory was not convinced. After ordering a variety of private blood tests, she discovered she was infected with a range of bacteria in the genus Borrelia that live in the guts of ticks, the infectious agents responsible for Lyme disease.
“It made sense,” she says. “Looking back, I was bitten in high school and misdiagnosed with mononucleosis. This was probably the start, and my immune system kept it under wraps for a while. The Lyme bacteria can burrow into every tissue in the body, go into cyst form and become dormant before reactivating.”
The reason why cases of Lyme disease are increasing is down to changing weather patterns, triggered by climate change, meaning that ticks are now found across a much wider geographic range than ever before.
When these species of bacteria are transmitted to humans, they can attack the nervous system, joints and even internal organs which can lead to serious health complications such as arthritis, meningitis and even heart failure. While Lyme disease can sometimes be successfully treated with antibiotics if spotted early on, not everyone responds to these drugs, and for patients who have developed chronic symptoms, there is no known cure. Flory says she knows of fellow Lyme disease patients who have spent hundreds of thousands of dollars seeking treatments.
Concerningly, statistics show that Lyme and other tick-borne diseases are on the rise. Recently released estimates based on health insurance records suggest that at least 476,000 Americans are diagnosed with Lyme disease every year, and many experts believe the true figure is far higher.
The reason why the numbers are growing is down to changing weather patterns, triggered by climate change, meaning that ticks are now found across a much wider geographic range than ever before. Health insurance data shows that cases of Lyme disease have increased fourfold in rural parts of the U.S. over the last 15 years, and 65 percent in urban regions.
As a result, many scientists who have studied Lyme disease feel that it is paramount to bring some form of protective vaccine to market which can be offered to people living in the most at-risk areas.
“Even the increased awareness for Lyme disease has not stopped the cases,” says Eva Sapi, professor of cellular and molecular biology at the University of New Haven. “Some of these patients are looking for answers for years, running from one doctor to another, so that is obviously a very big cost for our society at so many levels.”
Emerging vaccines – and backlash
But with the rising case numbers, interest has grown among the pharmaceutical industry and research communities. Vienna-based biotech Valneva have partnered with Pfizer to take their vaccine – a seasonal jab which offers protection against the six most common strains of Lyme disease in the northern hemisphere – into a Phase III clinical trial which began in August. Involving 6,000 participants in a number of U.S. states and northern Europe where Lyme disease is endemic, it could lead to a licensed vaccine by 2025, if it proves successful.
“For many years Lyme was considered a small market vaccine,” explains Monica E. Embers, assistant professor of parasitology at Tulane University in New Orleans. “Now we know that this is a much bigger problem, Pfizer has stepped up to invest in preventing this disease and other pharmaceutical companies may as well.”
Despite innovations, patient communities and their representatives remain ambivalent about the idea of a vaccine. Some of this skepticism dates back to the failed LYMErix vaccine which was developed in the late 1990s before being withdrawn from the market.
At the same time, scientists at Yale University are developing a messenger RNA vaccine which aims to train the immune system to respond to tick bites by exposing it to 19 proteins found in tick saliva. Whereas the Valneva vaccine targets the bacteria within ticks, the Yale vaccine attempts to provoke an instant and aggressive immune response at the site of the bite. This causes the tick to fall off and limits the potential for transmitting dangerous infections.
But despite these innovations, patient communities and their representatives remain ambivalent about the idea of a vaccine. Some of this skepticism dates back to the failed LYMErix vaccine which was developed in the late 1990s before being withdrawn from the market in 2002 after concerns were raised that it might induce autoimmune reactions in humans.
While this theory was ultimately disproved, the lingering stigma attached to LYMErix meant that most vaccine manufacturers chose to stay away from the disease for many years, something which Gregory Poland, head of the Mayo Clinic’s Vaccine Research Group in Minnesota, describes as a tragedy.
“Since 2002, we have not had a human Lyme vaccine in the U.S. despite the increasing number of cases,” says Poland. “Pretty much everyone in the field thinks they’re ten times higher than the official numbers, so you’re probably talking at least 400,000 each year. It’s an incredible burden but because of concerns about anti-vax protestors, until very recently, no manufacturer has wanted to touch this.”
Such was the backlash surrounding the failed LYMErix program that scientists have even explored the most creative of workarounds for protecting people in tick-populated regions, without needing to actually vaccinate them. One research program at the University of Tennessee came up with the idea of leaving food pellets containing a vaccine in woodland areas with the idea that rodents would eat the pellets, and the vaccine would then kill Borrelia bacteria within any ticks which subsequently fed on the animals.
Even the Pfizer-Valneva vaccine has been cautiously designed to try and allay any lingering concerns, two decades after LYMErix. “The concept is the same as the original LYMErix vaccine, but it has been made safer by removing regions that had the potential to induce autoimmunity,” says Embers. “There will always be individuals who oppose vaccines, Lyme or otherwise, but it will be a tremendous boost to public health to have the option.”
Vaccine alternatives
Researchers are also considering alternative immunization approaches in case sufficiently large numbers of people choose to reject any Lyme vaccine which gets approved. Researchers at UMass Chan Medical School have developed an artificially generated antibody, administered via an annual injection, which is capable of killing Borrelia bacteria in the guts of ticks before they can get into the human host.
So far animal studies have shown it to be 100 percent effective, while the scientists have completed a Phase I trial in which they tested it for safety on 48 volunteers in Nebraska. Because this approach provides the antibody directly, rather than triggering the human immune system to produce the antibody like a vaccine would, Embers predicts that it could be a viable alternative for the vaccine hesitant as well as providing an option for immunocompromised individuals who cannot produce enough of their own antibodies.
At the same time, many patient groups still raise concerns over the fact that numerous diagnostic tests for Lyme disease have been reported to have a poor accuracy. Without this, they argue that it is difficult to prove whether vaccines or any other form of immunization actually work. “If the disease is not understood enough to create a more accurate test and a universally accepted treatment protocol, particularly for those who weren’t treated promptly, how can we be sure about the efficacy of a vaccine?” says Natasha Metcalf, co-founder of the organization Lyme Disease UK.
Flory points out that there are so many different types of Borrelia bacteria which cause Lyme disease, that the immunizations being developed may only stop a proportion of cases. In addition, she says that chronic Lyme patients often report a whole myriad of co-infections which remain poorly understood and are likely to also be involved in the disease process.
Marci Flory undergoes an infusion in an attempt to treat her Lyme disease symptoms.
Marci Flory
“I would love to see an effective Lyme vaccine but I have my reservations,” she says. “I am infected with four types of Borrelia bacteria, plus many co-infections – Babesia, Bartonella, Erlichiosis, Rickettsia, and Mycoplasma – all from a single Douglas County Kansas tick bite. Lyme never travels alone and the vaccine won’t protect against all the many strains of Borrelia and co-infections.”
Valneva CEO Thomas Lingelbach admits that the Pfizer-Valneva vaccine is not perfect, but predicts that it will still have significant impact if approved.
“We expect the vaccine to have 75 percent plus efficacy,” he says. “There is this legacy around the old Lyme vaccines, but the world is very, very different today. The number of clinical manifestations known to be caused by infection with Lyme Borreliosis has significantly increased, and the understanding around severity has certainly increased.”
Embers agrees that while it will still be important for doctors to monitor for other tick-borne infections which are not necessarily covered by the vaccine, having any clinically approved jab would still represent a major step forward in the fight against the disease.
“I think that any vaccine must be properly vetted, and these companies are performing extensive clinical trials to do just that,” she says. “Lyme is the most common tick-borne disease in the U.S. so the public health impact could be significant. However, clinicians and the general public must remain aware of all of the other tick-borne diseases such as Babesia and Anaplasma, and continue to screen for those when a tick bite is suspected.”
AI was integral to creating Moderna's mRNA vaccine against COVID.
But the truth is that before ChatGPT nabbed the public’s attention, AI was already here, and it was doing more important things than writing essays for lazy college students. Case in point: It was key to saving the lives of tens of millions of people.
AI-designed mRNA vaccines
As Dave Johnson, chief data and AI officer at Moderna, told MIT Technology Review‘s In Machines We Trust podcast in 2022, AI was integral to creating the company’s highly effective mRNA vaccine against COVID. Moderna and Pfizer/BioNTech’s mRNA vaccines collectively saved between 15 and 20 million lives, according to one estimate from 2022.
Johnson described how AI was hard at work at Moderna, well before COVID arose to infect billions. The pharmaceutical company focuses on finding mRNA therapies to fight off infectious disease, treat cancer, or thwart genetic illness, among other medical applications. Messenger RNA molecules are essentially molecular instructions for cells that tell them how to create specific proteins, which do everything from fighting infection, to catalyzing reactions, to relaying cellular messages.
Johnson and his team put AI and automated robots to work making lots of different mRNAs for scientists to experiment with. Moderna quickly went from making about 30 per month to more than one thousand. They then created AI algorithms to optimize mRNA to maximize protein production in the body — more bang for the biological buck.
For Johnson and his team’s next trick, they used AI to automate science, itself. Once Moderna’s scientists have an mRNA to experiment with, they do pre-clinical tests in the lab. They then pore over reams of data to see which mRNAs could progress to the next stage: animal trials. This process is long, repetitive, and soul-sucking — ill-suited to a creative scientist but great for a mindless AI algorithm. With scientists’ input, models were made to automate this tedious process.
“We don’t think about AI in the context of replacing humans,” says Dave Johnson, chief data and AI officer at Moderna. “We always think about it in terms of this human-machine collaboration, because they’re good at different things. Humans are really good at creativity and flexibility and insight, whereas machines are really good at precision and giving the exact same result every single time and doing it at scale and speed.”
All these AI systems were in put in place over the past decade. Then COVID showed up. So when the genome sequence of the coronavirus was made public in January 2020, Moderna was off to the races pumping out and testing mRNAs that would tell cells how to manufacture the coronavirus’s spike protein so that the body’s immune system would recognize and destroy it. Within 42 days, the company had an mRNA vaccine ready to be tested in humans. It eventually went into hundreds of millions of arms.
Biotech harnesses the power of AI
Moderna is now turning its attention to other ailments that could be solved with mRNA, and the company is continuing to lean on AI. Scientists are still coming to Johnson with automation requests, which he happily obliges.
“We don’t think about AI in the context of replacing humans,” he told the Me, Myself, and AI podcast. “We always think about it in terms of this human-machine collaboration, because they’re good at different things. Humans are really good at creativity and flexibility and insight, whereas machines are really good at precision and giving the exact same result every single time and doing it at scale and speed.”
Moderna, which was founded as a “digital biotech,” is undoubtedly the poster child of AI use in mRNA vaccines. Moderna recently signed a deal with IBM to use the company’s quantum computers as well as its proprietary generative AI, MoLFormer.
Moderna’s success is encouraging other companies to follow its example. In January, BioNTech, which partnered with Pfizer to make the other highly effective mRNA vaccine against COVID, acquired the company InstaDeep for $440 million to implement its machine learning AI across its mRNA medicine platform. And in May, Chinese technology giant Baidu announced an AI tool that designs super-optimized mRNA sequences in minutes. A nearly countless number of mRNA molecules can code for the same protein, but some are more stable and result in the production of more proteins. Baidu’s AI, called “LinearDesign,” finds these mRNAs. The company licensed the tool to French pharmaceutical company Sanofi.
Writing in the journal Accounts of Chemical Research in late 2021, Sebastian M. Castillo-Hair and Georg Seelig, computer engineers who focus on synthetic biology at the University of Washington, forecast that AI machine learning models will further accelerate the biotechnology research process, putting mRNA medicine into overdrive to the benefit of all.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
