Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses

doi:10.1126/science.adi2396

. 2024 Dec 20;386(6728):1389-1395.

doi: 10.1126/science.adi2396. Epub 2024 Dec 19.

Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses

Vamsee Mallajosyula¹, Saborni Chakraborty^{1

2}, Elsa Sola¹, Ryan Furuichi Fong¹, Vishnu Shankar³, Fei Gao¹, Allison R Burrell⁴, Neha Gupta¹, Lisa E Wagar^{1

5}, Paul S Mischel^{6

7}, Robson Capasso⁸, Mary A Staat⁴, Yueh-Hsiu Chien^{1

9}, Cornelia L Dekker^{1

10}, Taia T Wang^{1

2}, Mark M Davis^{1

9

11}

Affiliations

¹ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA, USA.
³ Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Pediatrics, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁵ Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
⁶ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
⁸ Division of Sleep Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.

PMID: 39700292
DOI: 10.1126/science.adi2396

Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses

Vamsee Mallajosyula et al. Science. 2024.

. 2024 Dec 20;386(6728):1389-1395.

doi: 10.1126/science.adi2396. Epub 2024 Dec 19.

Authors

Affiliations

¹ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA, USA.
³ Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Pediatrics, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁵ Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
⁶ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
⁸ Division of Sleep Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.

PMID: 39700292
DOI: 10.1126/science.adi2396

Abstract

The seasonal influenza vaccine contains strains of viruses from distinct subtypes that are grown independently and then combined. However, most individuals exhibit a more robust response to one of these strains and thus are vulnerable to infection by others. By studying a monozygotic twin cohort, we found that although prior exposure is a factor, host genetics are a stronger driver of subtype bias to influenza viral strains. We found that covalent coupling of heterologous hemagglutinin (HA) from different viral strains could largely eliminate subtype bias in an animal model and in a human tonsil organoid system. We proposed that coupling of heterologous antigens improves antibody responses across influenza strains by broadening T cell help, and we found that using this approach substantially improved the antibody response to avian influenza HA.

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Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses

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Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses

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