tetano
Editor, Senior Moderator
Hum Vaccin Immunother
. 2022 Jun 15;2082191.
doi: 10.1080/21645515.2022.2082191. Online ahead of print.
Novel H7N9 influenza immunogen design enhances mobilization of seasonal influenza T cell memory in H3N2 pre-immune mice
Leonard Moise[SUP] 1 2 [/SUP], Lauren M Meyers[SUP] 1 [/SUP], Hyesun Jang[SUP] 2 [/SUP], Mayara Grizotte-Lake[SUP] 1 [/SUP], Christine M Boyle[SUP] 1 [/SUP], Bethany McGonnigal[SUP] 1 [/SUP], Pan Ge[SUP] 2 [/SUP], Ted M Ross[SUP] 2 3 [/SUP], Anne S De Groot[SUP] 1 2 [/SUP]
Affiliations
Abstract
Strategies that improve influenza vaccine immunogenicity are critical for the development of vaccines for pandemic preparedness. Hemagglutinin (HA)-specific CD4[SUP]+[/SUP] T cell epitopes support protective B cell responses against seasonal influenza. However, in the case of avian H7N9, which poses a pandemic threat, HA elicits only weak neutralizing antibody responses in infection and vaccination without adjuvant. We hypothesized that an immune-engineered H7N9 HA incorporating a broadly reactive H3N2 HA-specific memory CD4[SUP]+[/SUP] T cell epitope that replaces a regulatory T cell-inducing epitope at the corresponding position in H7N9 HA could harness preexisting influenza T cell immunity to increase CD4[SUP]+[/SUP] T cells that are needed for protective antibody development. We designed and produced a virus-like particle (VLP) vaccine that carries the epitope augmented H7N9 HA (OPT1) and immunized HLA-DR3 transgenic mice with established H3N2 immunity. OPT1-VLPs stimulated higher stem cell, central, and effector memory CD4[SUP]+[/SUP] T cell levels over wild type VLP immunization. In addition, activated, IL-21-producing follicular helper T cell frequencies were enhanced. This novel immunogen design strategy illustrates that site-specific modifications aimed to augment T cell epitope content enhance CD4[SUP]+[/SUP] T cell responses among critical subpopulations capable of aiding protective immune responses upon antigen re-encounter and that mobilization of immune memory can be used to overcome the poor immunogenicity of avian influenza viruses.
Keywords: H7N9; T cell; T cell epitope; Vaccine; hemagglutinin; immunoinformatics; influenza; virus-like particle.
. 2022 Jun 15;2082191.
doi: 10.1080/21645515.2022.2082191. Online ahead of print.
Novel H7N9 influenza immunogen design enhances mobilization of seasonal influenza T cell memory in H3N2 pre-immune mice
Leonard Moise[SUP] 1 2 [/SUP], Lauren M Meyers[SUP] 1 [/SUP], Hyesun Jang[SUP] 2 [/SUP], Mayara Grizotte-Lake[SUP] 1 [/SUP], Christine M Boyle[SUP] 1 [/SUP], Bethany McGonnigal[SUP] 1 [/SUP], Pan Ge[SUP] 2 [/SUP], Ted M Ross[SUP] 2 3 [/SUP], Anne S De Groot[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35704783
- DOI: 10.1080/21645515.2022.2082191
Abstract
Strategies that improve influenza vaccine immunogenicity are critical for the development of vaccines for pandemic preparedness. Hemagglutinin (HA)-specific CD4[SUP]+[/SUP] T cell epitopes support protective B cell responses against seasonal influenza. However, in the case of avian H7N9, which poses a pandemic threat, HA elicits only weak neutralizing antibody responses in infection and vaccination without adjuvant. We hypothesized that an immune-engineered H7N9 HA incorporating a broadly reactive H3N2 HA-specific memory CD4[SUP]+[/SUP] T cell epitope that replaces a regulatory T cell-inducing epitope at the corresponding position in H7N9 HA could harness preexisting influenza T cell immunity to increase CD4[SUP]+[/SUP] T cells that are needed for protective antibody development. We designed and produced a virus-like particle (VLP) vaccine that carries the epitope augmented H7N9 HA (OPT1) and immunized HLA-DR3 transgenic mice with established H3N2 immunity. OPT1-VLPs stimulated higher stem cell, central, and effector memory CD4[SUP]+[/SUP] T cell levels over wild type VLP immunization. In addition, activated, IL-21-producing follicular helper T cell frequencies were enhanced. This novel immunogen design strategy illustrates that site-specific modifications aimed to augment T cell epitope content enhance CD4[SUP]+[/SUP] T cell responses among critical subpopulations capable of aiding protective immune responses upon antigen re-encounter and that mobilization of immune memory can be used to overcome the poor immunogenicity of avian influenza viruses.
Keywords: H7N9; T cell; T cell epitope; Vaccine; hemagglutinin; immunoinformatics; influenza; virus-like particle.