Influenza vaccine based on AS03-adjuvanted chimeric HA induces long-lived stalk-specific plasma cells in bone marrow and lymph nodes of nonhuman primates
Current influenza vaccines face challenges due to antigenic evolution of the circulating virus and waning immunity in humans. Here we investigated the durability of humoral immunity induced by an influenza vaccine based on AS03-adjuvanted chimeric hemagglutinin (cHA) in nonhuman primates (NHPs). Two groups of NHPs received two doses of a seasonal quadrivalent influenza vaccine, followed by sequential immunization with split virus cHA vaccines cH8/1N1, and cH5/1N1. One group received cHA immunizations with AS03 adjuvant. We monitored serum antibodies and long-lived plasma cells in bone marrow for nearly 2 years after the final vaccination. cHA vaccines induced stalk-specific antibody responses. The addition of AS03 enhanced both the magnitude and durability of humoral immunity by establishing long-lived plasma cells in the bone marrow and lymph nodes for nearly 2 years. Passive transfer of NHP serum provided protection against challenge with heterologous influenza A virus strains in mice. This study highlights the potential of the AS03-adjuvanted chimeric HA vaccine strategy to provide durable and broadly protective humoral immunity.
Authors
- Peter Palese (ORCID: https://orcid.org/0000-0002-0337-5823)
- Gregory K. Tharp (ORCID: https://orcid.org/0000-0003-3075-755X)
- André Nicolás León (ORCID: https://orcid.org/0000-0001-5926-8966)
- Juan Manuel Carreño (ORCID: https://orcid.org/0000-0002-9039-9275)
- Rafi Ahmed (ORCID: https://orcid.org/0000-0002-9591-2621)
- Shirin Strohmeier
- Rama Rao Amara (ORCID: https://orcid.org/0000-0002-6309-6797)
- James A. Ferguson (ORCID: https://orcid.org/0000-0003-2891-0850)
- Akil Akhtar (ORCID: https://orcid.org/0000-0002-9069-6827)
- Julianna Han (ORCID: https://orcid.org/0000-0002-3402-2609)
- Sara T. Richey (ORCID: https://orcid.org/0000-0001-7854-1833)
- Rustom Antia (ORCID: https://orcid.org/0000-0001-7991-614X)
- Uchurappa Mala
- Hasan Ahmed
- Gabriele Neumann (ORCID: https://orcid.org/0000-0001-7054-1775)
- Anass Abbad (ORCID: https://orcid.org/0000-0002-4617-0473)
- Florian Krammer (ORCID: https://orcid.org/0000-0003-4121-776X)
- Chunyang Gu (ORCID: https://orcid.org/0000-0003-1283-1701)
- Yoshihiro Kawaoka (ORCID: https://orcid.org/0000-0001-5061-8296)
- Tiffany M. Styles (ORCID: https://orcid.org/0000-0002-0102-6566)
- Carl W. Davis (ORCID: https://orcid.org/0000-0002-6049-0684)
- Cora Hirst
- Kasey Stokdyk
Institutions
- Scripps Research Institute (US)
- University of Wisconsin–Madison (US)
- Emory University (US)
- Emory and Henry College (US)
- National Center for Global Health and Medicine (JP)
- Ludwig Boltzmann Institute Applied Diagnostics (AT)
- The University of Tokyo (JP)
- Medical University of Vienna (AT)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Immunology
- Published
- 2025-10-15
- DOI
- https://doi.org/10.1038/s41590-025-02309-1
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00