Any Point in Time

Any Point in Time

Study results offer glimpse into the future of forecasting infection and immunity

When TGen Assistant Professor, John
Altin, Ph.D., discusses PepSeq in terms of his latest study, you hear the excitement of discovery in his voice.

The PepSeq technology allows scientists to look across the universe of human-infecting viruses to determine precisely which infections someone has encountered and when, all from less than one microliter of blood plasma or serum. Overall, advancements like these have greatly expanded our ability to study diseases and viruses, providing the potential to lead to new breakthroughs that are changing how we interact with and interpret the world around us; foreshadowing the possibility of the day such technology enables surveillance of disease, much like a weather forecast.

A recent study led by Altin developed a new way of analyzing antibody signatures in repeat blood samples, enabling them to pinpoint the timing and cause of recent infections across the full suite of viruses that infected humans, simultaneously.  Using a powerful lab platform called PepSeq, Altin and a team of scientists used this new approach to detect epidemic waves of infection at the population level, as well as the rise and fall of antibody responses within individuals.

Published in Nature Communications, the findings suggest that PepSeq could one day allow for a far more complete picture of how infection and immunity move across a population in space and time.

“PepSeq allows us to look across the universe of human-infecting viruses to determine precisely which infections someone has encountered and when,” said Altin.  “The real power lies in the fact that we can get all this information from drop-size blood samples, tested over time.”

Altin and Jason Ladner, Ph.D., a colleague at Northern Arizona University, designed PepSeq to do just that. PepSeq profiles viral antibodies by designing a “library” of peptides of interest—short strings of amino acids that are the building blocks of proteins. By linking each peptide to a unique DNA tag, the scientists are able to pinpoint specific peptides targeted by specific antibodies (or other proteins) in a given sample.

Traditional analyses of this type can only track the response of an antibody to one peptide target at a time. PepSeq 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 used a single sample to map the whole history of viral exposures,” said TGen North bioinformatician and the study’s first author Erin Kelley (pictured at left), “but no information about when each virus was encountered.”

By analyzing blood samples collected over time, the researchers were able to pinpoint when infections occurred and how antibody responses evolved.

To generate the data, the research team collaborated with researchers in Cape Town, South Africa. They 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.

“We detected 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,” said Altin.

They also detected Rubella virus —German measles— within the ACS population, a disease not routinely targeted by childhood vaccination in South Africa. 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. This technology is very well adapted to screening across that kind of broad diversity, and PepSeq’s rapid turnaround time and scalability make it an attractive tool for researchers in a variety of fields.

“The new approach could revolutionize the way in which we monitor disease outbreaks and help us better understand how infections and immunity spread across populations. By detecting epidemic waves of infection at the population level as well as the rise and fall of antibody responses within individuals, PepSeq offers a far more comprehensive view of infectious disease than ever before,” said Altin.

Altin and his colleagues want to expand the PepSeq system to create even longer peptides for the libraries, including full-length proteins or domains, which could allow them to identify aspects of the response that are currently unseen.