tetano
Editor, Senior Moderator
Immun Ageing
. 2022 May 23;19(1):22.
doi: 10.1186/s12979-022-00282-z.
Poly-γ-glutamic acid/Alum adjuvanted pH1N1 vaccine-immunized aged mice exhibit a significant increase in vaccine efficacy with a decrease in age-associated CD8 [SUP]+[/SUP] T cell proportion in splenocytes
Jihyun Yang[SUP] #[/SUP][SUP] 1 [/SUP], Jaemoo Kim[SUP] #[/SUP][SUP] 1 2 [/SUP], Chaewon Kwak[SUP] 1 2 [/SUP], Haryoung Poo[SUP] 3 4 [/SUP]
Affiliations
Abstract
Background: Highly contagious respiratory diseases caused by viral infections are a constantly emerging threat, particularly the elderly with the higher risk of developing serious complications. Vaccines are the best strategy for protection against influenza-related diseases. However, the elderly has lower vaccine efficacy than young population and the age-driven decline of the influenza vaccine efficacy remains unresolved.
Objectives: This study investigates the effect of an adjuvant, poly-γ-glutamic acid and alum (PGA/Alum) on vaccine efficacy in aged mice (18-months) and its mechanism is investigated using ovalbumin as a model antigen and a commercial pandemic H1N1 (pH1N1) flu vaccine. Antigen trafficking, dendritic cell (DC) activation, and the DC-mediated T cell activation were analyzed via in vivo imaging and flow cytometry. Antigen-specific humoral and cellular immune responses were evaluated in sera and splenocytes from the vaccinated mice. Also, we analyzed gene expression profiles of splenocytes from the vaccinated mice via single-cell transcriptome sequencing and evaluated the protective efficacy against pH1N1 virus challenge.
Results: Aged mice had lower antigen trafficking and DC activation than younger mice (6-weeks), which was ameliorated by PGA/Alum with increased antigen uptake and DC activation leading to improved antigen-specific IFN-γ[SUP]+[/SUP]CD8[SUP]+[/SUP] T lymphocyte frequencies higher in the vaccinated aged mice, to a similar extent as PGA/Alum adjuvanted vaccine-immunized young mice. The results of single-cell transcriptome sequencing display that PGA/Alum also reduced the proportion of age-associated CD8[SUP]+[/SUP] T cell subsets and gene levels of inhibitory regulators in CD8[SUP]+[/SUP] T cells, which may play a role in the recovery of CD8[SUP]+[/SUP] T cell activation. Finally, PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice were completely protected (100% survival) compared to aged mice immunized with vaccine only (0% survival) after pH1N1 virus challenge, akin to the efficacy of the vaccinated young mice (100% survival).
Conclusions: PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice showed a significant increase in vaccine efficacy compared to aged mice administered with vaccine only. The enhanced vaccine efficacy by PGA/Alum is associated with significant increases of activation of DCs and effector CD8[SUP]+[/SUP] T cells and a decrease in age-associated CD8[SUP]+[/SUP] T cell proportion of splenocytes. Collectively, PGA/Alum adjuvanted flu vaccine may be a promising vaccine candidate for the elderly.
Keywords: Aging; CD8+ T lymphocyte; Dendritic cells; Influenza virus; Vaccine adjuvant; γ-PGA.
. 2022 May 23;19(1):22.
doi: 10.1186/s12979-022-00282-z.
Poly-γ-glutamic acid/Alum adjuvanted pH1N1 vaccine-immunized aged mice exhibit a significant increase in vaccine efficacy with a decrease in age-associated CD8 [SUP]+[/SUP] T cell proportion in splenocytes
Jihyun Yang[SUP] #[/SUP][SUP] 1 [/SUP], Jaemoo Kim[SUP] #[/SUP][SUP] 1 2 [/SUP], Chaewon Kwak[SUP] 1 2 [/SUP], Haryoung Poo[SUP] 3 4 [/SUP]
Affiliations
- PMID: 35606855
- DOI: 10.1186/s12979-022-00282-z
Abstract
Background: Highly contagious respiratory diseases caused by viral infections are a constantly emerging threat, particularly the elderly with the higher risk of developing serious complications. Vaccines are the best strategy for protection against influenza-related diseases. However, the elderly has lower vaccine efficacy than young population and the age-driven decline of the influenza vaccine efficacy remains unresolved.
Objectives: This study investigates the effect of an adjuvant, poly-γ-glutamic acid and alum (PGA/Alum) on vaccine efficacy in aged mice (18-months) and its mechanism is investigated using ovalbumin as a model antigen and a commercial pandemic H1N1 (pH1N1) flu vaccine. Antigen trafficking, dendritic cell (DC) activation, and the DC-mediated T cell activation were analyzed via in vivo imaging and flow cytometry. Antigen-specific humoral and cellular immune responses were evaluated in sera and splenocytes from the vaccinated mice. Also, we analyzed gene expression profiles of splenocytes from the vaccinated mice via single-cell transcriptome sequencing and evaluated the protective efficacy against pH1N1 virus challenge.
Results: Aged mice had lower antigen trafficking and DC activation than younger mice (6-weeks), which was ameliorated by PGA/Alum with increased antigen uptake and DC activation leading to improved antigen-specific IFN-γ[SUP]+[/SUP]CD8[SUP]+[/SUP] T lymphocyte frequencies higher in the vaccinated aged mice, to a similar extent as PGA/Alum adjuvanted vaccine-immunized young mice. The results of single-cell transcriptome sequencing display that PGA/Alum also reduced the proportion of age-associated CD8[SUP]+[/SUP] T cell subsets and gene levels of inhibitory regulators in CD8[SUP]+[/SUP] T cells, which may play a role in the recovery of CD8[SUP]+[/SUP] T cell activation. Finally, PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice were completely protected (100% survival) compared to aged mice immunized with vaccine only (0% survival) after pH1N1 virus challenge, akin to the efficacy of the vaccinated young mice (100% survival).
Conclusions: PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice showed a significant increase in vaccine efficacy compared to aged mice administered with vaccine only. The enhanced vaccine efficacy by PGA/Alum is associated with significant increases of activation of DCs and effector CD8[SUP]+[/SUP] T cells and a decrease in age-associated CD8[SUP]+[/SUP] T cell proportion of splenocytes. Collectively, PGA/Alum adjuvanted flu vaccine may be a promising vaccine candidate for the elderly.
Keywords: Aging; CD8+ T lymphocyte; Dendritic cells; Influenza virus; Vaccine adjuvant; γ-PGA.