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

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.

Fighting flu: novel CD8+ T‐cell targets are required for future influenza vaccines

“… 34 VLPs are generated by expressing viral proteins derived from structural proteins. 58 , 59 When expressed, a phenomenon occurs where viral proteins fold and form an outer structure of a virus. 58 , 59 From there, viral antigens, like HA and NA proteins, can be expressed and bound to the surface of the viral architecture.…”

“… 58 , 59 When expressed, a phenomenon occurs where viral proteins fold and form an outer structure of a virus. 58 , 59 From there, viral antigens, like HA and NA proteins, can be expressed and bound to the surface of the viral architecture. 58 , 59 , 60 An advantage of VLP is that they do not contain viral genetic material, which makes them relatively safe as they cannot undergo viral replication.…”

“… 58 , 59 From there, viral antigens, like HA and NA proteins, can be expressed and bound to the surface of the viral architecture. 58 , 59 , 60 An advantage of VLP is that they do not contain viral genetic material, which makes them relatively safe as they cannot undergo viral replication. 58 VLP can be administered intramuscularly and have made highly successful vaccines against viruses in the past such as human papillomaviruses (HPV).…”

Immunogenicity and protective efficacy of an influenza virus-like particle-based SARS-CoV-2 hybrid vaccine candidate in rhesus macaques

“…It is possible that Flu VLP might have acted as an adjuvant before infection resulting in a better bystander effect upon challenge with the SARS-CoV-2. We have recently shown that Flu VLP induces a cross-protective effect against heterologous influenza viruses without inducing hemagglutination inhibiting antibody response (50). Therefore, further studies are needed to understand the potential cross-protection between influenza and SARS-CoV-2 and the associated mechanisms.…”