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

Science. 2024 Dec 20;386(6728):1389-1395. doi: 10.1126/science.adi2396. Epub 2024 Dec 19.

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.

MeSH terms

  • Animals
  • Antibodies, Viral* / immunology
  • Antibody Formation / immunology
  • Antigens, Viral* / immunology
  • CD4-Positive T-Lymphocytes* / immunology
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus* / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus* / immunology
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A virus / genetics
  • Influenza A virus / immunology
  • Influenza Vaccines* / immunology
  • Influenza, Human* / immunology
  • Influenza, Human* / prevention & control
  • Influenza, Human* / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organoids / immunology
  • Organoids / virology
  • Palatine Tonsil / immunology
  • Palatine Tonsil / virology

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines