A San Diego biotech trying to figure out why coronavirus vaccines work better for some people than others is searching for clues in an unlikely place: poop.
Persephone Biosciences is recruiting volunteers for a 250-person study that will look for links between vaccine efficacy and the microbiome: the diverse and dazzling community of bacteria that live inside your intestines.
There's good precedent for such a study. In 2019, Stanford scientists reported that healthy volunteers who took antibiotics before and after their flu shot had weaker antibody responses than untreated participants. Antibodies, which are Y-shaped proteins made by the immune system, are often the key to a successful vaccine response, as they can latch onto a virus and prevent infection.
There have been similar studies in the world of immunotherapy, which uses treatments that rev up the body's immune response against cancer cells. A pair of studies published by Israeli researchers and a joint effort between the National Institutes of Health and the University of Pittsburg showed that transferring stool from a melanoma patient who responded to treatment into someone who didn't helped shrink some participants' tumors. And with 1 trillion bacteria jam-packed into every gram of stool, that's a telltale sign that gut microbes can influence anti-cancer immune responses.
But why and how? Scientists are still pinning down precise answers, but there's growing evidence that gut bacteria communicate closely with nearby immune cells, responding to signals and sending some of their own via small molecules and metabolites that can travel widely through the body once they reach the bloodstream. When the cast of characters living in the gut changes, those signals change, too
"In people who do not respond to vaccines, or who do not respond to the latest cancer drugs, what we're finding is a very severely damaged gut microbiome," said Stephanie Culler, CEO of Persephone.
The biotech plans to collect stool and blood samples from volunteers before and after they receive a COVID-19 vaccine, relying on a stool self-collection kit and a phlebotomist who will travel to participants' homes to draw blood. The samples will then be analyzed to identify the various bacterial species present and what small molecules they're making. The company will also order sequencing on viral samples from participants who test positive for COVID-19.
All participants will receive $300 for their time, and those who test positive for the coronavirus and send in a nasal swab for sequencing will get an additional $100.
All of that data will feed into an artificial intelligence algorithm that will look for links between participants' microbiomes and whether they developed COVID-19.
There's no guarantee the company will find anything. After all, whether someone gets COVID-19 after being vaccinated could simply have to do with the amount of virus they were exposed to, or whether they were infected before they were fully immunized. But Culler is hoping the pilot study, which is being done in Southern California, will show an early, promising link to the microbiome.
If that's the case, Persephone will ramp up to a 10,000-person national study and explore probiotic treatments that introduce bacterial species meant to promote a stronger vaccine response. Culler says the company is already working on such a treatment, though it has yet to be tested in clinical trials.
"The vision there is that you go in and get your vaccine and you get a blister pack of one to two weeks of our pills, and you should be good to go," she said.
To learn more about the study or to enroll, visit www.join-voices.com.
