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Q+A: Why Do Vaccines Work More In Some People Than in Others?

Patient receiving vaccine

Patient receiving vaccine

Patient receiving a vaccine

The breathtaking pace of development for COVID-19 vaccines showed what was possible with enough resources. Subsequent development of the vaccines is a reminder that viruses are a moving target that is ever-changing. Vaccines for COVID-19, malaria, the flu, and many other diseases must constantly adapt to these changes to protect recipients from disease. But how can researchers anticipate which participants in a clinical trial will gain immunity days after they get a dose of a vaccine?

Thanks to a new study in Nature Immunology, researchers have gained insights into why some people develop immunity to a disease following vaccination, while others do not. To do this, they studied 13 different vaccines, such as flu, hepatitis A/B, and smallpox. Using vast swaths of data – 3,000 samples from 820 adults making up 28 studies — the researchers, from more than 20 institutions nationwide, including Drexel University’s College of Medicine, pinpointed specific genes expressed in antibody responses to all but one of the vaccines studied a week after vaccination. The authors refer to these unique patterns of antibody response as “signatures.”

Each vaccine produced a unique response signature within a week of vaccinations, the only exception being the yellow fever vaccine, in which antibody-producing stem cells, known as plasmablasts, took 2-3 times longer to be released in the body. According to the researchers, this is possibly because the shot contains live virus.

After adjusting for time of immune response, the authors found a common predictor – a specific group of genes found in an antibody response known as M156.1 – that was associated with the subsequent antibody response after being vaccinated.

When a vaccine is administered, a genetic blueprint of, or an actual weakened or inactive part of an antigen — such as a virus or bacterium — is injected into the body. Vaccines do not cause disease. Instead, they tell the immune system to react as if it were attacking the actual virus or pathogen — thereby training the body to ward off the actual virus or bacteria when they’re encountered.

This most recent work follows two other studies on human immunology that worked to standardize data across studies from The National Institutes of Health’s Human Immunology Project Consortium, which was started in 2010 to study the human immune system.

The hope is that compiling this vaccine-reaction data into an “atlas of immunology” resource can improve future vaccine testing and development.

The Drexel News Blog checked in with Elias El Haddad, PhD, a professor in the College of Medicine, and member of The Human Immunology Project Consortium that performed the study.

What’s the important takeaway for non-researchers here? How does this study advance our understanding of the variation of human responses to certain vaccines?

This study has been conducted on a large number of volunteers and encompassed 13 different vaccines. The study showed no evidence of universal signature — meaning no universal gene expression before and after vaccination to predict how the body responded — however, it identified a roadmap of vaccine responses that can be used as an atlas for vaccine responses. More importantly, the study identified a unique dynamic of antibody response that was shown to be common amongst all vaccines tested in this study.

How close is the field to a PCR test – similar to the lab technology used to detect whether an individual has COVID-19 – that could be used during clinical trials of vaccines to pinpoint biomarkers and help predict immune responses?

We are progressing at an outstanding pace for reaching this goal. With the new technologies in assay development and bioinformatics we are inching closer towards a vaccine chip development.

How might insights from this study help researchers in evaluating future vaccines?

The amount of bioinformatics data generated from this study is overwhelming. The study provided insight into the immunology, metabolism, proteomics and antibody pathways that represent a gold mind for researchers that can inspire novel ideas and generate hypotheses.

What’s next in this work for you and your colleagues?

Work on validation of molecules and pathways identified in this study and further move into testing these in training study cohorts.

Anything else important to mention?

This study has also addressed the impact of aging on vaccine response. This is extremely important considering the reduced vaccine responses to flu and COVID-19 vaccines in aging individuals.

Media interested in talking to El Haddad should contact Greg Richter, news manager, at or 215.895.2614.

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