tetano
Editor, Senior Moderator
Immun Ageing
. 2023 May 11;20(1):20.
doi: 10.1186/s12979-023-00344-w. Hemagglutinin virus-like particles incorporated with membrane-bound cytokine adjuvants provide protection against homologous and heterologous influenza virus challenge in aged mice
Bo Ryoung Park[SUP] 1 [/SUP], Ramireddy Bommireddy[SUP] 2 [/SUP], David Hyunjung Chung[SUP] 1 [/SUP], Ki-Hye Kim[SUP] 1 [/SUP], Jeeva Subbiah[SUP] 1 [/SUP], Yu-Jin Jung[SUP] 1 [/SUP], Noopur Bhatnagar[SUP] 1 [/SUP], Christopher D Pack[SUP] 3 [/SUP], Sampath Ramachandiran[SUP] 3 [/SUP], Shaker J C Reddy[SUP] 3 [/SUP], Periasamy Selvaraj[SUP] 2 [/SUP], Sang-Moo Kang[SUP] 4 [/SUP]
Affiliations
Background: Current influenza vaccines deliver satisfactory results in young people but are less effective in the elderly. Development of vaccines for an ever-increasing aging population has been an arduous challenge due to immunosenescence that impairs the immune response in the aged, both quantitatively and qualitatively.
Results: To potentially enhance vaccine efficacy in the elderly, we investigated the immunogenicity and cross-protection of influenza hemagglutinin virus-like particles (HA-VLP) incorporated with glycosylphosphatidylinositol (GPI)-anchored cytokine-adjuvants (GPI-GM-CSF and GPI-IL-12) via protein transfer in aged mice. Lung viral replication against homologous and heterologous influenza viruses was significantly reduced in aged mice after vaccination with cytokine incorporated VLPs (HA-VLP-Cyt) in comparison to HA-VLP alone. Enhanced IFN-γ[SUP]+[/SUP]CD4[SUP]+[/SUP] and IFN-γ[SUP]+[/SUP]CD8[SUP]+[/SUP] T cell responses were also observed in aged mice immunized with HA-VLP-Cyt when compared to HA-VLP alone.
Conclusions: Cytokine-adjuvanted influenza HA-VLP vaccine induced enhanced protective response against homologous influenza A virus infection in aged mice. Influenza HA-VLP vaccine with GPI-cytokines also induced enhanced T cell responses correlating with better protection against heterologous infection in the absence of neutralizing antibodies. The results suggest that a vaccination strategy using cytokine-adjuvanted influenza HA-VLPs could be used to enhance protection against influenza A virus in the elderly.
Keywords: Aged mice; Cross protection; Cytokine adjuvants; GPI-GM-CSF; GPI-IL-12; HA-VLP; Hemagglutinin (HA); Influenza; T cells; Virus-like particles (HA-VLPs).
. 2023 May 11;20(1):20.
doi: 10.1186/s12979-023-00344-w. Hemagglutinin virus-like particles incorporated with membrane-bound cytokine adjuvants provide protection against homologous and heterologous influenza virus challenge in aged mice
Bo Ryoung Park[SUP] 1 [/SUP], Ramireddy Bommireddy[SUP] 2 [/SUP], David Hyunjung Chung[SUP] 1 [/SUP], Ki-Hye Kim[SUP] 1 [/SUP], Jeeva Subbiah[SUP] 1 [/SUP], Yu-Jin Jung[SUP] 1 [/SUP], Noopur Bhatnagar[SUP] 1 [/SUP], Christopher D Pack[SUP] 3 [/SUP], Sampath Ramachandiran[SUP] 3 [/SUP], Shaker J C Reddy[SUP] 3 [/SUP], Periasamy Selvaraj[SUP] 2 [/SUP], Sang-Moo Kang[SUP] 4 [/SUP]
Affiliations
- PMID: 37170231
- DOI: 10.1186/s12979-023-00344-w
Background: Current influenza vaccines deliver satisfactory results in young people but are less effective in the elderly. Development of vaccines for an ever-increasing aging population has been an arduous challenge due to immunosenescence that impairs the immune response in the aged, both quantitatively and qualitatively.
Results: To potentially enhance vaccine efficacy in the elderly, we investigated the immunogenicity and cross-protection of influenza hemagglutinin virus-like particles (HA-VLP) incorporated with glycosylphosphatidylinositol (GPI)-anchored cytokine-adjuvants (GPI-GM-CSF and GPI-IL-12) via protein transfer in aged mice. Lung viral replication against homologous and heterologous influenza viruses was significantly reduced in aged mice after vaccination with cytokine incorporated VLPs (HA-VLP-Cyt) in comparison to HA-VLP alone. Enhanced IFN-γ[SUP]+[/SUP]CD4[SUP]+[/SUP] and IFN-γ[SUP]+[/SUP]CD8[SUP]+[/SUP] T cell responses were also observed in aged mice immunized with HA-VLP-Cyt when compared to HA-VLP alone.
Conclusions: Cytokine-adjuvanted influenza HA-VLP vaccine induced enhanced protective response against homologous influenza A virus infection in aged mice. Influenza HA-VLP vaccine with GPI-cytokines also induced enhanced T cell responses correlating with better protection against heterologous infection in the absence of neutralizing antibodies. The results suggest that a vaccination strategy using cytokine-adjuvanted influenza HA-VLPs could be used to enhance protection against influenza A virus in the elderly.
Keywords: Aged mice; Cross protection; Cytokine adjuvants; GPI-GM-CSF; GPI-IL-12; HA-VLP; Hemagglutinin (HA); Influenza; T cells; Virus-like particles (HA-VLPs).