Genetic signature quickly predicts who will develop vaccine immunity

Genetic signature quickly predicts who will develop vaccine immunity

A genetic signature seen in antibody-producing cells in the blood of vaccinated study participants could speed up vaccine development, a new study suggests.

Scientists developing COVID-19 vaccines accelerated clinical trials, but a major stalemate was waiting to see if the vaccine protected study participants. What if there was a way to predict a person’s vaccine-induced immunity?

By studying the immune responses of 820 adults to 13 vaccines, researchers found that the best predictor of immunity for many vaccines was a recognizable genetic signature in blood cells that produce antibodies – plasmablasts – seven days after vaccination. .

With the discovery of such a universal predictor of immunity to vaccination, scientists hope to accelerate vaccine development by measuring the genetic signature of plasmablasts in a person within days of vaccination, rather than waiting weeks for see if that person’s immune system will respond appropriately. .

“Our integrated analysis revealed a common genetic signature that predicts the strength of the antibody response to most vaccines,” says Bali Pulendran, professor of microbiology and immunology at Stanford University and lead author of the study in Natural immunology.

“This paves the way for the development of a ‘chip vaccine’ that can be used as an early screening strategy for future vaccine candidates, thereby accelerating the timeline of research and development efforts.”

Vaccination Immunity Atlas

Pulendran has been pondering the idea of ​​a universal predictor of immunity ever since he wrote a paper in 2008 reviewing the yellow fever vaccine, a vaccine with 97% efficacy, which is considered a gold standard to understand how an effective vaccine works.

He and his colleagues studied cells, genes and proteins to see how they responded to the yellow fever vaccine. Using machine learning, the researchers found biomarkers, molecular signs that vaccines were working, within the first week after vaccination, that could predict the antibody immune response at 30, 60 and 90 days.

The article launched the field of systems vaccinology, a comprehensive look at the molecular landscape of vaccine response. Following the 2008 paper, researchers explored other vaccines, such as influenza, malaria, and meningococcal and pneumococcal vaccines, producing a 2021 study also led by Pulendran detailing the Pfizer-BioNTech mRNA vaccine COVID-19. They identified the molecular machinery initiated by each vaccine, but the research left open whether there was a universal predictor.

To find the common marker in the current study, the researchers created a “Vaccine Immunity Atlas,” a compilation of previously published genomic readouts of molecular material, including plasmablast genes, produced once the system a person’s immune system is activated by a particular vaccine. This is the most comprehensive dataset on vaccine responses collected, Pulendran says.

“This molecular atlas of immunity to vaccination serves as a kind of immune fingerprinting registry to cross-reference for all future vaccines that scientists will develop to anticipate the immunity of patients who will receive the vaccine.”

When people are vaccinated, their immune response follows a classic deployment: the foreign object (antigen) activates white blood cells that make antibodies and attack invaders (B cells) as well as cells that destroy traitors to the body ( T cells), which can then turn into memory cells, before disappearing once the immune system disarms the invader.

Finding commonality between study participants’ vaccines is possible because our immune system responses tend to vary, even slightly, from vaccine to vaccine. Our innate immune response is old and simple: Barriers, such as the skin, that prevent foreign bodies from entering our bodies are common, from “sea slugs to stockbrokers,” says Pulendran.

But it takes about seven days for our adaptive immune response — the one we know best, which includes antibodies and memories of pathogens gone bad — to kick in.

In their study, the scientists found that key elements of participants’ vaccine-induced immune cascade were similar in all but one vaccine: yellow fever. The yellow fever immune response followed the same pathway as the other vaccine responses, but with a delay in plasmablast deployment time.

Pulendran says it’s likely because it’s a live vaccine that builds a slow progression of immune response, the way a symphony progresses by adding one instrument at a time after the conductor’s baton is raised. of orchestra.

Once the scientists adjusted for time, the algorithm revealed the predictor of a person’s response to virtually any vaccine: the plasmablast signature, specifically M156.1, a specific module or set of genes expressed in plasmablasts.

‘Vaccine chip’ in the future?

In their study, Pulendran and his colleagues proposed a “vaccine chip” that would use a PCR test – what lab technicians use to find the genetic material of the COVID-19 virus – to measure a set of genes that predict the outcome of a vaccine response by studying which genes are activated and therefore which immune products are present in the body. The study suggests that if your plasmablast M156.1 gene reading reaches a threshold level, you are more likely to be protected against the targeted pathogen.

Scientists could incorporate the chip into clinical trials to speed up their evaluation of candidate vaccines. Clinicians may also be able to use the chip to predict an immunocompromised person’s response to a vaccine to see if they need a booster sooner than most.

Although the study found a threshold of immunity, at the peak of the antibody response, among the participants, it does not suggest how long the immunity will last. Pulendran and his colleagues are now focused on finding a universal predictor of durability to understand how long we can go until we need new vaccine boosters.

“We are in an exciting new era in this area of ​​systems vaccinology, with the prospect of personalizing vaccines for the recipient based on these molecular signatures,” says Pulendran.

“The COVID-19 pandemic has underscored the global imperative to be ready to accelerate the deployment of multiple candidate vaccines when the next pandemic emerges. This is a big step in the right direction.

Other researchers come from the Icahn School of Medicine at Mount Sinai, Emory University School of Medicine, National Institutes of Health, University of Cambridge, UC San Francisco, Fred Hutchinson Cancer Research Center, from Boston Children’s Hospital, Harvard Medical School, NG Health Solutions, Broad Institute of MIT and Harvard, University of Lausanne and Swiss Institute of Bioinformatics.

National Institutes of Health; the Department of Pediatrics at Boston Children’s Hospital; the Bill and Melinda Gates Foundation; Open philanthropy; and the Violetta L. Horton, Soffer, and Open Philanthropy foundations funded the work.

Source: Stanford University

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