tetano
Editor, Senior Moderator
Cell Rep Med
. 2025 Sep 25:102369.
doi: 10.1016/j.xcrm.2025.102369. Online ahead of print. Chimeric hemagglutinin-based universal influenza mRNA vaccine induces protective immunity and bone marrow plasma cells in rhesus macaques
Tiffany M Styles[SUP] 1 [/SUP], Akil Akhtar[SUP] 1 [/SUP], Chunyang Gu[SUP] 2 [/SUP], Gabriele Neumann[SUP] 2 [/SUP], Hiromi Muramatsu[SUP] 3 [/SUP], Justine S McPartlan[SUP] 4 [/SUP], Poulami Talukder[SUP] 4 [/SUP], Derrik Gratz[SUP] 5 [/SUP], Kasey Stokdyk[SUP] 5 [/SUP], Hannah L Turner[SUP] 6 [/SUP], James A Ferguson[SUP] 6 [/SUP], Alesandra J Rodriguez[SUP] 6 [/SUP], Madhumathi Loganathan[SUP] 7 [/SUP], Benjamin Francis[SUP] 7 [/SUP], Anass Abbad[SUP] 7 [/SUP], Ghania Chikh[SUP] 8 [/SUP], Ying K Tam[SUP] 8 [/SUP], Zhaohui S Qin[SUP] 9 [/SUP], Julianna Han[SUP] 6 [/SUP], Juan Manuel Carreño[SUP] 7 [/SUP], Andrew B Ward[SUP] 6 [/SUP], Jasdave S Chahal[SUP] 4 [/SUP], Christian W Mandl[SUP] 4 [/SUP], Norbert Pardi[SUP] 3 [/SUP], Yoshihiro Kawaoka[SUP] 10 [/SUP], Florian Krammer[SUP] 11 [/SUP], Rafi Ahmed[SUP] 1 [/SUP], Rama R Amara[SUP] 12 [/SUP]
Affiliations
A universal influenza vaccine that elicits a strong and lasting stalk-specific antibody response is advantageous. We utilize nucleoside-modified mRNA in lipid nanoparticles (mRNA-LNP) and unmodified self-amplifying mRNA in modified dendritic nanoparticles (sam-MDNP), expressing chimeric hemagglutinin (cHA) antigens to induce stalk-specific humoral immunity in non-human primates with pre-existing influenza virus immunity. mRNA-LNP immunization induces strong stalk-specific binding antibodies capable of protecting mice from lethal heterologous influenza virus challenges and bone marrow plasma cells (BMPCs) that persist for up to 8 months. sam-MDNP vaccine induces lower humoral immunity, despite showing strong innate activation. Transcriptomic and cytokine analyses reveal a more persistent induction of interferon responses, interleukin (IL)-1β signaling, and IL-6 production in the mRNA-LNP group, correlating with the induction of serum antibody responses and BMPCs. These results identify a transcriptional signature associated with induction of BMPCs following mRNA vaccination and highlight the utility of cHA-based mRNA-LNP vaccines in inducing persistent stalk-directed protective antibody responses.
Keywords: bone marrow plasma cells; chimeric hemagglutinin; mRNA-LNP; rhesus macaques; self-amplifying mRNA; transcriptional signatures; universal influenza vaccine.
. 2025 Sep 25:102369.
doi: 10.1016/j.xcrm.2025.102369. Online ahead of print. Chimeric hemagglutinin-based universal influenza mRNA vaccine induces protective immunity and bone marrow plasma cells in rhesus macaques
Tiffany M Styles[SUP] 1 [/SUP], Akil Akhtar[SUP] 1 [/SUP], Chunyang Gu[SUP] 2 [/SUP], Gabriele Neumann[SUP] 2 [/SUP], Hiromi Muramatsu[SUP] 3 [/SUP], Justine S McPartlan[SUP] 4 [/SUP], Poulami Talukder[SUP] 4 [/SUP], Derrik Gratz[SUP] 5 [/SUP], Kasey Stokdyk[SUP] 5 [/SUP], Hannah L Turner[SUP] 6 [/SUP], James A Ferguson[SUP] 6 [/SUP], Alesandra J Rodriguez[SUP] 6 [/SUP], Madhumathi Loganathan[SUP] 7 [/SUP], Benjamin Francis[SUP] 7 [/SUP], Anass Abbad[SUP] 7 [/SUP], Ghania Chikh[SUP] 8 [/SUP], Ying K Tam[SUP] 8 [/SUP], Zhaohui S Qin[SUP] 9 [/SUP], Julianna Han[SUP] 6 [/SUP], Juan Manuel Carreño[SUP] 7 [/SUP], Andrew B Ward[SUP] 6 [/SUP], Jasdave S Chahal[SUP] 4 [/SUP], Christian W Mandl[SUP] 4 [/SUP], Norbert Pardi[SUP] 3 [/SUP], Yoshihiro Kawaoka[SUP] 10 [/SUP], Florian Krammer[SUP] 11 [/SUP], Rafi Ahmed[SUP] 1 [/SUP], Rama R Amara[SUP] 12 [/SUP]
Affiliations
- PMID: 41005301
- DOI: 10.1016/j.xcrm.2025.102369
A universal influenza vaccine that elicits a strong and lasting stalk-specific antibody response is advantageous. We utilize nucleoside-modified mRNA in lipid nanoparticles (mRNA-LNP) and unmodified self-amplifying mRNA in modified dendritic nanoparticles (sam-MDNP), expressing chimeric hemagglutinin (cHA) antigens to induce stalk-specific humoral immunity in non-human primates with pre-existing influenza virus immunity. mRNA-LNP immunization induces strong stalk-specific binding antibodies capable of protecting mice from lethal heterologous influenza virus challenges and bone marrow plasma cells (BMPCs) that persist for up to 8 months. sam-MDNP vaccine induces lower humoral immunity, despite showing strong innate activation. Transcriptomic and cytokine analyses reveal a more persistent induction of interferon responses, interleukin (IL)-1β signaling, and IL-6 production in the mRNA-LNP group, correlating with the induction of serum antibody responses and BMPCs. These results identify a transcriptional signature associated with induction of BMPCs following mRNA vaccination and highlight the utility of cHA-based mRNA-LNP vaccines in inducing persistent stalk-directed protective antibody responses.
Keywords: bone marrow plasma cells; chimeric hemagglutinin; mRNA-LNP; rhesus macaques; self-amplifying mRNA; transcriptional signatures; universal influenza vaccine.