Hemagglutinin virus-like particles incorporated with membrane-bound cytokine adjuvants provide protection against homologous and heterologous influenza virus challenge in aged mice

• Type of Material: Article
• Authors: Bo Ryoung Park, Georgia State University; Ramireddy Bommireddy, Emory University; David Hyunjung Chung, Georgia State University; Ki-Hye Kim, Georgia State University; Jeeva Subbiah, Georgia State University; Yu-Jin Jung, Georgia State University; Noopur Bhatnagar, Georgia State University; Christopher D Pack, Metaclipse Therapeutics Corporation, Atlanta; Sampath Ramachandiran, Metaclipse Therapeutics Corporation, Atlanta; Shaker JC Reddy, Metaclipse Therapeutics Corporation, Atlanta; Periasamy Selvaraj, Emory University; Sang-Moo Kang, Georgia State University
• Language: English
• Date: 2023-05-11
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12979-023-00344-w
• Title of Journal or Parent Work: IMMUNITY & AGEING
• Volume: 20
• Issue: 1
• Start Page: 20
• End Page: 20
• Grant/Funding Information: NIH/NIAID (SBIR Contract# 75N93019C00017 to Pack/Ramachandiran; 1 R01 AI154656 to SMK).
• Keywords: DENDRITIC CELLS; Geriatrics & Gerontology; PROTEIN TRANSFER; COLONY-STIMULATING FACTOR; IMMUNE-RESPONSES; GM-CSF; Influenza; Hemagglutinin (HA); Virus-like particles (HA-VLPs); ELDERLY ADULTS; Immunology; INTERLEUKIN-12; GPI-GM-CSF; GPI-IL-12; Cross protection; EFFICACY; T cells; VACCINE; Science & Technology; TUMOR-ASSOCIATED ANTIGENS; Life Sciences & Biomedicine; Cytokine adjuvants; Aged mice; HA-VLP
• Research Categories: Health Sciences, Pathology

Abstract

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+CD4+ and IFN-γ+CD8+ 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.