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150 research primates got diarrhea, flooding lab with priceless vaccine data
Researchers now have clear new targets and insights for developing a Shigella vaccine.
Having more than 150 non-human primates at a research center fall ill with diarrhea in a stomach-churning outbreak that flowed for over two years doesn’t sound much like good fortune. But for some scientists, it kind of was, providing a heaping pile of valuable data on how they might finally defeat a foul foe.
In a study published in the latest issue of Science Translational Medicine, scientist sifted through the dump of immunological data from the infections, logging new ways to train immune cells to defeat the bacteria behind the outbreak, a type of Shigella. Researchers were able to pluck out specific bits of the bacteria that the immune system could most effectively attack, linking specific target molecules to specific types of germ-busting immune responses. The researchers even precisely homed in on some of the tiny notches within those craggy target molecules where the most potent antibodies attached.
In all, the study “revealed unexpected features of the anti-Shigella antibody response in naturally infected [non-human primates] and represents a step toward the rational design of Shigella vaccine candidates,” the authors write.
Shigella is a gastrointestinal horror, striking more than 200 million people in the world each year and killing more than 200,000, mostly children. Those who survive typically develop some protective immune responses. But, given that there are various species and serotypes of Shigella, protective immune responses tend to only work against a narrow range of the bacteria’s family. And, on top of that, Shigella strains are only becoming more resistant to antibiotics.
The need for a Shigella vaccine—one that can combat the whole cruddy clan—is clear. As such, there are many vaccine development efforts underway. Still, scientists have been toiling without some of the detailed molecular and structural data needed to design a sophisticated vaccine. That’s where the outbreak came in.
The outbreak began in December 2022 at the Wisconsin National Primate Research Center in Madison. Non-human primates are natural hosts for Shigella, like humans, and it’s not uncommon for outbreaks to flare at such facilities now and then. But it is unusual for an outbreak to be so big and last so long. Even some of the people who worked at the facility fell ill.
In all, there were 169 microbiologically confirmed shigellosis cases among the non-human primates. Researchers collected 151 Shigella isolates for serotyping and did whole genome sequencing on 95 representative isolates. The outbreak was caused by two related clusters of Shigella flexneri, a species that commonly strikes captive non-human primates. (Human outbreaks are more often driven by Shigella sonnei, but both species can infect either type of primate.) Of the 90 isolates tested for antimicrobial resistance, more than half (63 percent) were multidrug resistant. Most of the cases caused only mild diarrheal symptoms, but there were some asymptomatic cases and some cases that led to severe symptoms. Infants were the hardest hit, similar to what’s seen in humans.
The researchers drew serum, plasma, and specific types of immune cells from 41 infected animals across their infections, taking samples at 1, 2, and between 4 to 6 weeks after an infection was detected. Then they went to work dissecting the immune responses.
The researchers started by looking for antibodies that attacked a known target on Shigella, the O-antigen. This is the outermost component of a large molecule that juts out from the bacteria’s outermost membrane. The molecule is called LPS, or lipopolysaccharide. LPS is found exclusively on bacteria, specifically Gram-negative bacteria, a group that includes E. coli, Salmonella, and Shigella. The molecule functions as a structural component of the outer membrane, among other things. But given its position on the rim of these bacterial cells, it—and specifical