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Nat Immunol
. 2025 Oct 15.
doi: 10.1038/s41590-025-02309-1. Online ahead of print. Influenza vaccine based on AS03-adjuvanted chimeric HA induces long-lived stalk-specific plasma cells in bone marrow and lymph nodes of nonhuman primates
Akil Akhtar # 1 2 , Tiffany M Styles # 1 2 , Chunyang Gu 3 , André Nicolás León 4 , Gregory K Tharp 1 , Kasey Stokdyk 1 2 , Anass Abbad 5 6 , Cora Hirst 7 , Shirin Strohmeier 5 , Gabriele Neumann 3 , Sara T Richey 4 , James A Ferguson 4 , Uchurappa Mala 1 2 , Hasan Ahmed 7 , Julianna Han 4 , Juan Manuel Carreño 5 6 , Carl W Davis 1 2 , Rustom Antia 7 , Peter Palese 5 , Andrew B Ward 4 , Yoshihiro Kawaoka 3 8 9 10 , Florian Krammer 5 6 11 12 13 , Rafi Ahmed 1 2 , Rama R Amara 14 15
Affiliations
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.
. 2025 Oct 15.
doi: 10.1038/s41590-025-02309-1. Online ahead of print. Influenza vaccine based on AS03-adjuvanted chimeric HA induces long-lived stalk-specific plasma cells in bone marrow and lymph nodes of nonhuman primates
Akil Akhtar # 1 2 , Tiffany M Styles # 1 2 , Chunyang Gu 3 , André Nicolás León 4 , Gregory K Tharp 1 , Kasey Stokdyk 1 2 , Anass Abbad 5 6 , Cora Hirst 7 , Shirin Strohmeier 5 , Gabriele Neumann 3 , Sara T Richey 4 , James A Ferguson 4 , Uchurappa Mala 1 2 , Hasan Ahmed 7 , Julianna Han 4 , Juan Manuel Carreño 5 6 , Carl W Davis 1 2 , Rustom Antia 7 , Peter Palese 5 , Andrew B Ward 4 , Yoshihiro Kawaoka 3 8 9 10 , Florian Krammer 5 6 11 12 13 , Rafi Ahmed 1 2 , Rama R Amara 14 15
Affiliations
- PMID: 41094203
- DOI: 10.1038/s41590-025-02309-1
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.