A new technique reveals ‘viral history’ in a single blood test

• The test consists of a single analysis of a drop of blood. That highly reduces the cost comparing to existing serological methods, which are limited to analyze a single virus in each test.
• Samples of 569 people in the US, Peru, Thailand and South Africa were analyzed to develop VirScan.
• IrsiCaixa ICREA researcher Christian Brander collaborated in the study, coordinated by scientists of the Harvard Medical School in Boston. 

Each virus entering the human body leaves a nearly indelible immune footprint. Besides of causing diseases, a virus changes forever the host immune system by developing antibodies, and may also predispose the person to develop other diseases in the future. Understanding the interaction between the immune system and the set of viruses that infect humans, known as viroma, may have clinical implications and help the research of new vaccines. Science journal publishes a study on the development of a new technique, VirScan, which allows, with a single drop of blood, to draw the viral landscape a person has been exposed to throughout his life. IrsiCaixa ICREA researcher Christian Brander collaborated in the study, coordinated by scientists of the Harvard Medical School in Boston. Part of the funding came from the HIVACAT AIDS vaccine research project.

Currently, to detect a specific virus it is necessary a doctor sets a clinical hypothesis and orders a test. This new technology allows to identify all viruses a person has been exposed to, either through infection or vaccination, with a single analysis and an approximate price of $ 25. The test characterizes the full spectrum of responses generated by the immune system cells that produce antibodies against the virus, so-called B cells.

"Knowing the footprints left by infections in the immune system will tell us how this past will determine the immune response to new virus attacks," explains Christian Brander, IrsiCaixa ICREA researcher. "The big challenge to develop new treatments is finding out which antibodies protect us against a disease, but before we have to know what antibodies we already have in the body".

For example, having a "high resolution photograph" of the immune response of HIV-people could be useful to design vaccines to induce antibodies against the virus in the future: "We could analyze the B cells response of people who control the infection on their own, without antiretroviral treatment (so-called “controllers”), and check what part of their answer is different from people who cannot control the infection”, says Brander. "That has implications not only for preventive vaccine, but also for therapeutic", he adds. VirScan is also easily expandable to integrate other pathogens such as bacteria, fungi and protozoa.

When a microorganism is introduced in the human body, the immune system triggers a response to eliminate it. After controlling the infection, the immune system creates specific memory response that is able to record the pathogen. Thus, if the infectious agent reappears, the immune system can respond much more quickly, preventing the disease from developing. A vaccine is a substance that teaches the immune system to recognize and defend us against viruses or bacteria that cause disease. The immune system recognizes the vaccine agents as foreign, so when the pathogen appears, it is already prepared to respond.

Differences between populations 

To develop VirScan, scientists created a library of peptides –short fragments of virus-derived protein- representing 206 virus and 1,000 strains. They then analysed blood samples from 569 people in 4 countries: USA, Peru, South Africa and Thailand. The samples were divided into groups according to age, geographic location and whether or not they were carriers of HIV, but scientists found that the vast majority of immune systems recognized the same small number of peptides. This pattern suggests that the immune system of many individuals hits the same viral protein, which might have important implications for understanding the immune system and the development of vaccines.

The results detected antibodies to an average of 10 virus per person. The most frequent virus were those that commonly infect humans, such as cytomegalovirus and Epstein-Barr (infectious mononucleosis virus) and Rhinovirus (common cold virus). 88'1% of the samples tested positive for Epstein-Barr; 75'2% for Rhinovirus B; 73,9% for Rhinovirus A; 58'4% for Influenza A; 37.3% for polio (due to vaccination) and 24.4% for varicella zoster.

VirScan analysis revealed that, in general, people living outside the US had higher frequencies of virus exposure or infection, probably due to differences in population density, cultural practices, sanitation or genetic susceptibility. Instead, seropositivity in Influenza B (seasonal flu virus) was higher in the US, probably because of the higher rates of vaccination. Other viruses, such as rhinovirus and Epstein-Barr virus, were detected with similar frequencies in all populations.

Studies on HIV

Furthermore, when comparing results between HIV positive and negative people, it was found that HIV people were more frequently positive for other viruses, including HSV2 (genital herpes virus), cytomegalovirus and Kaposi sarcoma-associated herpesvirus (a skin cancer common in HIV people). That confirms earlier studies indicating a higher level of co-infection in HIV people. Previously unknown serological differences, as a greater presence of antibodies against Adenovirus B (associated with colds, conjunctivitis, diphtheria, bronchitis or pneumonia) or respiratory syncytial virus were also found. These results can provide information about how HIV infection alters the balance between host immunity and viruses, and also help to identify pathogens that may increase susceptibility to HIV and other infections.

Brander points out the possibility that a cohort of Barcelona, integrated by people monitored every 2-3 months because of their high risk of exposure to HIV, might be included in the study in the near future. "We want to understand what factor or factors make they don’t become infected when they are exposed to the virus", explains the researcher.