tetano
Editor, Senior Moderator
EBioMedicine
. 2024 May 27:104:105153.
doi: 10.1016/j.ebiom.2024.105153. Online ahead of print. A chimeric haemagglutinin-based universal influenza virus vaccine boosts human cellular immune responses directed towards the conserved haemagglutinin stalk domain and the viral nucleoprotein
Carly M Bliss[SUP] 1 [/SUP], Raffael Nachbagauer[SUP] 2 [/SUP], Chiara Mariottini[SUP] 2 [/SUP], Frans Cuevas[SUP] 2 [/SUP], Jodi Feser[SUP] 3 [/SUP], Abdi Naficy[SUP] 3 [/SUP], David I Bernstein[SUP] 4 [/SUP], Jeffrey Guptill[SUP] 5 [/SUP], Emmanuel B Walter[SUP] 6 [/SUP], Francesco Berlanda-Scorza[SUP] 3 [/SUP], Bruce L Innis[SUP] 3 [/SUP], Adolfo García-Sastre[SUP] 7 [/SUP], Peter Palese[SUP] 8 [/SUP], Florian Krammer[SUP] 9 [/SUP], Lynda Coughlan[SUP] 10 [/SUP]
Affiliations
Background: The development of a universal influenza virus vaccine, to protect against both seasonal and pandemic influenza A viruses, is a long-standing public health goal. The conserved stalk domain of haemagglutinin (HA) is a promising vaccine target. However, the stalk is immunosubdominant. As such, innovative approaches are required to elicit robust immunity against this domain. In a previously reported observer-blind, randomised placebo-controlled phase I trial (NCT03300050), immunisation regimens using chimeric HA (cHA)-based immunogens formulated as inactivated influenza vaccines (IIV) -/+ AS03 adjuvant, or live attenuated influenza vaccines (LAIV), elicited durable HA stalk-specific antibodies with broad reactivity. In this study, we sought to determine if these vaccines could also boost T cell responses against HA stalk, and nucleoprotein (NP).
Methods: We measured interferon-γ (IFN-γ) responses by Enzyme-Linked ImmunoSpot (ELISpot) assay at baseline, seven days post-prime, pre-boost and seven days post-boost following heterologous prime:boost regimens of LAIV and/or adjuvanted/unadjuvanted IIV-cHA vaccines.
Findings: Our findings demonstrate that immunisation with adjuvanted cHA-based IIVs boost HA stalk-specific and NP-specific T cell responses in humans. To date, it has been unclear if HA stalk-specific T cells can be boosted in humans by HA-stalk focused universal vaccines. Therefore, our study will provide valuable insights for the design of future studies to determine the precise role of HA stalk-specific T cells in broad protection.
Interpretation: Considering that cHA-based vaccines also elicit stalk-specific antibodies, these data support the further clinical advancement of cHA-based universal influenza vaccine candidates.
Funding: This study was funded in part by the Bill and Melinda Gates Foundation (BMGF).
Keywords: Haemagglutinin; Stalk; T cells; Universal influenza vaccine.
. 2024 May 27:104:105153.
doi: 10.1016/j.ebiom.2024.105153. Online ahead of print. A chimeric haemagglutinin-based universal influenza virus vaccine boosts human cellular immune responses directed towards the conserved haemagglutinin stalk domain and the viral nucleoprotein
Carly M Bliss[SUP] 1 [/SUP], Raffael Nachbagauer[SUP] 2 [/SUP], Chiara Mariottini[SUP] 2 [/SUP], Frans Cuevas[SUP] 2 [/SUP], Jodi Feser[SUP] 3 [/SUP], Abdi Naficy[SUP] 3 [/SUP], David I Bernstein[SUP] 4 [/SUP], Jeffrey Guptill[SUP] 5 [/SUP], Emmanuel B Walter[SUP] 6 [/SUP], Francesco Berlanda-Scorza[SUP] 3 [/SUP], Bruce L Innis[SUP] 3 [/SUP], Adolfo García-Sastre[SUP] 7 [/SUP], Peter Palese[SUP] 8 [/SUP], Florian Krammer[SUP] 9 [/SUP], Lynda Coughlan[SUP] 10 [/SUP]
Affiliations
- PMID: 38805853
- DOI: 10.1016/j.ebiom.2024.105153
Background: The development of a universal influenza virus vaccine, to protect against both seasonal and pandemic influenza A viruses, is a long-standing public health goal. The conserved stalk domain of haemagglutinin (HA) is a promising vaccine target. However, the stalk is immunosubdominant. As such, innovative approaches are required to elicit robust immunity against this domain. In a previously reported observer-blind, randomised placebo-controlled phase I trial (NCT03300050), immunisation regimens using chimeric HA (cHA)-based immunogens formulated as inactivated influenza vaccines (IIV) -/+ AS03 adjuvant, or live attenuated influenza vaccines (LAIV), elicited durable HA stalk-specific antibodies with broad reactivity. In this study, we sought to determine if these vaccines could also boost T cell responses against HA stalk, and nucleoprotein (NP).
Methods: We measured interferon-γ (IFN-γ) responses by Enzyme-Linked ImmunoSpot (ELISpot) assay at baseline, seven days post-prime, pre-boost and seven days post-boost following heterologous prime:boost regimens of LAIV and/or adjuvanted/unadjuvanted IIV-cHA vaccines.
Findings: Our findings demonstrate that immunisation with adjuvanted cHA-based IIVs boost HA stalk-specific and NP-specific T cell responses in humans. To date, it has been unclear if HA stalk-specific T cells can be boosted in humans by HA-stalk focused universal vaccines. Therefore, our study will provide valuable insights for the design of future studies to determine the precise role of HA stalk-specific T cells in broad protection.
Interpretation: Considering that cHA-based vaccines also elicit stalk-specific antibodies, these data support the further clinical advancement of cHA-based universal influenza vaccine candidates.
Funding: This study was funded in part by the Bill and Melinda Gates Foundation (BMGF).
Keywords: Haemagglutinin; Stalk; T cells; Universal influenza vaccine.