The work, recently published in the journal , reveals an underappreciated connection between genetics and our antibodies. Antibodies are key players in our immune system, with important roles in human health and disease, including in infection, autoimmunity, cancer and even vaccine responsiveness.

“Our work demonstrates that not everyone has the same capacity to generate certain types of antibodies due to genetics,” said Oscar Rodriguez, a post-doctoral fellow at UofL, and the first author of the study. “This could have critical implications for how we assess outcomes related to treatments and vaccines that depend on the antibody response.”

Vaccines, for example, work by simulating a viral infection and triggering an immune response — a sort of drill that teaches the body what a virus looks like and how to fight it. While it’s commonly known that individual response to vaccines can vary from person to person, this work shows more clearly than ever that these variations may depend on the antibody genes a person has inherited.

“For a long time, we’ve assumed vaccines could be designed using a one-size-fits-all approach,” said Melissa Smith, director of the , and lead author of the study. “This research shows that genetics predisposes us to qualitatively and quantitatively different antibody responses. If this information could be used to understand when individuals will or won’t respond to a given vaccine or treatment, that could be hugely impactful.”

The research also revealed that differences in our antibody responses could be linked to broader patterns of genetic diversity across human populations. This stresses the need to better characterize diversity in the genes that encode antibodies, and specifically increase the sampling of understudied populations. This is one of the driving forces behind research being conducted by this team.

Critical for advancing this effort is the recent acquisition of a by the Sequencing Technology Center. UofL is one of only a handful of��service providers in the country to offer access to this technology. Its use by this team could help improve our understanding of ancestry-specific immune gene-associated disease through the characterization of antibody genes in thousands of individuals worldwide, leading to improved and more equitable patient care.��

“We are currently building the most comprehensive catalogs of human antibody genetic variation from diverse genetic ancestries,” said Corey T. Watson, associate professor in the , and senior author of the study. “By studying a greater number of populations across the globe, we will be able to clarify the contribution genes make in positioning our immune systems to respond in a variety of disease contexts, and hopefully inform next-generation treatments.”

KYNETIC is a National Institutes of Health (NIH) funded Research Evaluation and Commercialization Hub (REACH) and part of the national NIH Proof-of-Concept Network. The program offers entrepreneurial education and proof-of-concept/product development grants to accelerate the translation of research innovations into biomedical products by investigators throughout the Commonwealth of Kentucky.�� ��

The goal is to advance the most promising biomedical research innovations — including pharmaceuticals, devices and apps — from the state’s eight public universities and the Kentucky Community & Technical College System (KCTCS).

In this cycle, KYNETIC awarded roughly $40,000 grants to each of the following research teams:

• Christina Ralph-Nearman and Cheri Levinson, University of Louisville
• Melissa Smith and Corey Watson, University of Louisville
• Stuart Williams, Maxwell Boakye and Michael Voor, University of Louisville
• Daniel Boamah, Kimberly Greene and Austin Griffiths, Western Kentucky University
• Jamie Fredericks, Eastern Kentucky University
• Mark Fritz and Guigen Zhang, University of Kentucky��
• Jill Kolesar and Chris Richards, University of Kentucky
• Brittany Levy, University of Kentucky

KYNETIC is led by UofL, the University of Kentucky, the Kentucky Cabinet for Economic Development and Kentucky Commercialization Ventures. Launched in 2019, the KYNETIC program builds on UofL’s strong history of translational research support, which includes a prestigious for turning research into products.

“These programs help to drive UofL research from lab to market – impactful research with the power to improve and even save lives,” said Jessica Sharon, UofL’s director of innovation programs who helps lead KYNETIC. “The UofL projects selected for KYNETIC funding in this cycle embody that goal.”

The pre-application window for KYNETIC’s Cycle 8 is currently open. The deadline is July 18, 2023, by 5 p.m. Pre-applications can be��.

KYNETIC Project Managers are available for consultation before you submit your pre-application and throughout the application process. You can find more information��.

Watson, along with UofL post-doctoral fellow Oscar Rodriguez, and visiting fellow Yana Safonova, are part of an international group of researchers who say the narrow studies limit their ability to identify variation in human adaptive immune responses across populations.

“We need to better understand how genetics influences immune system function by studying population cohorts that better represent the diversity observed across the globe if we are to fully understand disease susceptibility, as well as design more tailored treatments and preventative measures,” Watson said.

In an article published in Nature Methods, , the group advocates for resources used in immunogenomics research to actively include and specifically identify additional populations and minority groups. They say such diversity will make their research more relevant and help in understanding population and ancestry-specific gene-associated disease, leading to improvements in patient care.

“As scientists, we have a say in which populations are investigated. Therefore, it is critical for us to be actively inclusive of individuals representative of the world we live in. This is especially critical for genes that are as diverse and clinically relevant as those that encode antibodies and T cell receptors,” Rodriguez said.

Watson’s research focuses on immune function and molecular genetics. His team is studying a specific area of the genetic code that controls antibody function to better understand how differences in an individual’s genes determine their susceptibility to certain diseases or immune responses to vaccines.

In collaboration with Melissa Smith, assistant professor in the , the team is conducting the largest sequencing efforts of the antibody gene regions in humans and in animal models, Watson said.

“Specifically in humans, we are working to build catalogs of genetic variation in samples from multiple ethnic backgrounds and are engaged in projects that seek to understand how this genetic variation influences the immune response in infection, vaccination and other disease contexts,” he said.

Watson is involved in efforts to improve the resources and data standards for antibody and T cell receptor genes for immunogenomics researchers around the world.

The article in Nature Methods was co-authored by researchers from the United States, Canada, Norway, France, Sweden, the United Kingdom, Russia, Saudi Arabia, Israel, South Africa, Nigeria, Chile, Peru, China, Japan, Taiwan and French Polynesia with expertise in biomedical and translational research, population and public health genetics, health disparities and computational biology as well as immunogenomics.