tetano
Editor, Senior Moderator
Adv Sci (Weinh)
. 2023 Apr 24;e2206521.
doi: 10.1002/advs.202206521. Online ahead of print.
Lymph Node Follicle-Targeting STING Agonist Nanoshells Enable Single-Shot M2e Vaccination for Broad and Durable Influenza Protection
Hsiao-Han Tsai[SUP] 1 2 [/SUP], Ping-Han Huang[SUP] 3 [/SUP], Leon Cw Lin[SUP] 1 4 [/SUP], Bing-Yu Yao[SUP] 1 4 [/SUP], Wan-Ting Liao[SUP] 3 [/SUP], Chen-Hsueh Pai[SUP] 1 4 [/SUP], Yu-Han Liu[SUP] 1 [/SUP], Hui-Wen Chen[SUP] 3 [/SUP], Che-Ming J Hu[SUP] 1 2 4 5 [/SUP]
Affiliations
Abstract
The highly conserved matrix protein 2 ectodomain (M2e) of influenza viruses presents a compelling vaccine antigen candidate for stemming the pandemic threat of the mutation-prone pathogen, yet the low immunogenicity of the diminutive M2e peptide renders vaccine development challenging. A highly potent M2e nanoshell vaccine that confers broad and durable influenza protectivity under a single vaccination is shown. Prepared via asymmetric ionic stabilization for nanoscopic curvature formation, polymeric nanoshells co-encapsulating high densities of M2e peptides and stimulator of interferon genes (STING) agonists are prepared. Robust and long-lasting protectivity against heterotypic influenza viruses is achieved with a single administration of the M2e nanoshells in mice. Mechanistically, molecular adjuvancy by the STING agonist and nanoshell-mediated prolongation of M2e antigen exposure in the lymph node follicles synergistically contribute to the heightened anti-M2e humoral responses. STING agonist-triggered T cell helper functions and extended residence of M2e peptides in the follicular dendritic cell network provide a favorable microenvironment that induces Th1-biased antibody production against the diminutive antigen. These findings highlight a versatile nanoparticulate design that leverages innate immune pathways for enhancing the immunogenicity of weak immunogens. The single-shot nanovaccine further provides a translationally viable platform for pandemic preparedness.
Keywords: follicular dendritic cells; germinal center; lymph node follicle targeting; matrix protein 2 ectodomain antigen; nanoshell; stimulator of interferon genes agonist; universal influenza vaccine.
. 2023 Apr 24;e2206521.
doi: 10.1002/advs.202206521. Online ahead of print.
Lymph Node Follicle-Targeting STING Agonist Nanoshells Enable Single-Shot M2e Vaccination for Broad and Durable Influenza Protection
Hsiao-Han Tsai[SUP] 1 2 [/SUP], Ping-Han Huang[SUP] 3 [/SUP], Leon Cw Lin[SUP] 1 4 [/SUP], Bing-Yu Yao[SUP] 1 4 [/SUP], Wan-Ting Liao[SUP] 3 [/SUP], Chen-Hsueh Pai[SUP] 1 4 [/SUP], Yu-Han Liu[SUP] 1 [/SUP], Hui-Wen Chen[SUP] 3 [/SUP], Che-Ming J Hu[SUP] 1 2 4 5 [/SUP]
Affiliations
- PMID: 37092580
- DOI: 10.1002/advs.202206521
Abstract
The highly conserved matrix protein 2 ectodomain (M2e) of influenza viruses presents a compelling vaccine antigen candidate for stemming the pandemic threat of the mutation-prone pathogen, yet the low immunogenicity of the diminutive M2e peptide renders vaccine development challenging. A highly potent M2e nanoshell vaccine that confers broad and durable influenza protectivity under a single vaccination is shown. Prepared via asymmetric ionic stabilization for nanoscopic curvature formation, polymeric nanoshells co-encapsulating high densities of M2e peptides and stimulator of interferon genes (STING) agonists are prepared. Robust and long-lasting protectivity against heterotypic influenza viruses is achieved with a single administration of the M2e nanoshells in mice. Mechanistically, molecular adjuvancy by the STING agonist and nanoshell-mediated prolongation of M2e antigen exposure in the lymph node follicles synergistically contribute to the heightened anti-M2e humoral responses. STING agonist-triggered T cell helper functions and extended residence of M2e peptides in the follicular dendritic cell network provide a favorable microenvironment that induces Th1-biased antibody production against the diminutive antigen. These findings highlight a versatile nanoparticulate design that leverages innate immune pathways for enhancing the immunogenicity of weak immunogens. The single-shot nanovaccine further provides a translationally viable platform for pandemic preparedness.
Keywords: follicular dendritic cells; germinal center; lymph node follicle targeting; matrix protein 2 ectodomain antigen; nanoshell; stimulator of interferon genes agonist; universal influenza vaccine.