Host genetics play a significant role in shaping immune responses to different strains in the influenza vaccine, overshadowing the impact of previous viral exposures.
A newly developed vaccine platform shows promising results in boosting immunity against multiple influenza subtypes.
Host Genetics vs. Prior Flu Exposure
Most people who receive the seasonal flu vaccine, which targets multiple virus subtypes, develop a strong immune response to only one strain, leaving them vulnerable to others. Researchers have long debated whether host genetics or prior exposure to flu viruses has a greater impact on this uneven immune response. A recent study has found that host genetics plays a more significant role.
Global Impact of Influenza and Vaccine Challenges
The research team also introduced a new vaccine platform that boosted protection against multiple flu subtypes when tested in animal models and human organoids. Influenza remains a major global health challenge, causing hundreds of thousands of deaths and millions of hospitalizations each year. Most human infections come from specific influenza A subtypes (H1N1 and H3N2) and B lineages (Victoria and Yamagata), each containing multiple virus strains.
The Role of Immune Memory and Genetic Variation
However, many vaccinated individuals still respond more strongly to one strain, leaving them exposed to others. This effect is linked to a phenomenon known as “original antigenic sin” (OAS), where the immune system’s memory of its first flu encounter biases its response to future vaccines. Additionally, genetic variations in the human leukocyte antigen (HLA) system influence how the immune system processes and presents vaccine antigens, shaping immune responses.
Genetic Drivers of Vaccine Response Uncovered
To better understand the balance between genetics and prior exposure, Vamsee Mallajosyula and colleagues studied immune responses in monozygotic twins, vaccinated infants, and mouse models. They found that host genetics, especially major histocompatibility complex (MHC) class-II polymorphisms, primarily drives flu vaccine responses, with prior exposure playing a secondary role.
A New Vaccine Platform for Broader Protection
The researchers also developed a method to link antigens from different flu strains using a molecular scaffold, enhancing CD4+ T cell activation and broadening the immune response. Tests in mice and human tonsil organoids confirmed increased antibody production against various flu strains, including avian influenza, highlighting the potential for more effective flu vaccines.
Reference: “Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses” by Vamsee Mallajosyula, Saborni Chakraborty, Elsa Sola, Ryan Furuichi Fong, Vishnu Shankar, Fei Gao, Allison R. Burrell, Neha Gupta, Lisa E. Wagar, Paul S. Mischel, Robson Capasso, Mary A. Staat, Yueh-Hsiu Chien, Cornelia L. Dekker, Taia T. Wang and Mark M. Davis, 19 December 2024, Science.
DOI: 10.1126/science.adi2396
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1 Comment
This is how pandemics start, folks.