Results offer glimpse into the future of forecasting infection and immunity
PHOENIX, Ariz. — April 3, 2023 — By developing a new way of analyzing antibody signatures in repeat blood samples, researchers have shown they can pinpoint the timing and cause of recent infections across the full suite of viruses that infect humans, simultaneously.
The global team of scientists, led by researchers from the Translational Genomics Research Institute (TGen), part of City of Hope, used the new approach to detect epidemic waves of infection at the population level as well as the rise and fall of antibody responses within individuals.
The researchers used a powerful lab platform called PepSeq, which “allows us to look across the universe of human-infecting viruses to determine precisely which infections someone has encountered and when,” said senior author John Altin, Ph.D., Assistant Professor in TGen’s Pathogen Genomics and Integrated Cancer Genomics Divisions, and one of PepSeq’s creators. “We can get all this information from drop-size blood samples, tested over time.”
The findings published in Nature Communications suggests PepSeq “could one day be widely deployed in the surveillance of disease, much like a weather forecast, allowing us to generate a far more complete picture of how infection and immunity will move across a population in space and time,” Altin added.
PepSeq, which was developed as a tool for viral antibody profiling by scientists at TGen and Northern Arizona University (NAU), works by designing a “library” of peptides of interest—short strings of amino acids that are the building blocks of proteins. Each peptide is then linked to a unique DNA tag, which allows the scientists to pinpoint which peptides are being targeted by which antibodies (or other proteins) in a sample.
The technology allows researchers to track antibody response to thousands or hundreds of thousands of peptide targets at a time, making it ideal for examining the full range of viral infections within populations and individuals.
“Most previous work in this area has taken a snapshot approach, using a single sample to map the whole history of viral exposures,” said TGen North bioinformatician and the paper’s first author Erin Kelley, “but no information about when each virus was encountered.”
By analyzing blood samples collected over time, the researchers were able to add that time dimension, pinpointing when infections occurred and how antibody responses evolved.
The research team looked at blood samples collected from three different groups, with individuals ranging in age from 12 to 60+ years old and totaling more than 100 person-years’ worth of data.
One of the groups, the Adolescent Cohort Study (ACS), collected blood samples regularly for 18 months from tuberculosis-infected 12-18-year-olds in South Africa.
The researchers were able to detect natural epidemic waves in the ACS data, including outbreaks of the respiratory viruses Influenza A and Enterovirus D, as well as the gastrointestinal Aichivirus A, in some cases showing that the viruses were widely circulating before being noted in the population.
Rubella virus, which is not routinely targeted by childhood vaccination in South Africa, was also a notable infection in the ACS population.
The study revealed that antibody signatures remained detectable more than five years after an initial infection in some people. In other cases, the researchers saw antibody responses rise and fall again in an individual within a week or two.
These findings suggest “there may be opportunities to monitor someone’s immunological health, using these natural viral infections as a probe,” said Altin.
Research funding for the study comes from the National Institute of Allergy and Infectious Disease (U24 award U24AI152172).
# # #
About TGen, part of City of Hope
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based nonprofit organization dedicated to conducting groundbreaking research with life-changing results. TGen is part of City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children. Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help patients through efficiency and effectiveness of the translational process. Follow TGen on Facebook, LinkedIn and Twitter @TGen.