Poly-γ-glutamic acid/Alum adjuvanted pH1N1 vaccine-immunized aged mice exhibit a significant increase in vaccine...

Area of Science:

• Immunology
• Vaccinology
• Gerontology

Background:

• Highly contagious respiratory viral diseases pose a threat, especially to the elderly.
• Influenza vaccines are crucial, but their efficacy is reduced in older adults.
• Age-related decline in vaccine effectiveness remains a significant public health challenge.

Purpose of the Study:

• To investigate the adjuvant effect of poly-γ-glutamic acid and alum (PGA/Alum) on influenza vaccine efficacy in aged mice.
• To elucidate the underlying mechanisms of PGA/Alum's action on immune responses.
• To evaluate protection against pandemic H1N1 (pH1N1) flu virus challenge.

Main Methods:

• Utilized aged (18-month) and young (6-week) mice models.
• Administered ovalbumin and a pH1N1 flu vaccine, with and without PGA/Alum adjuvant.
• Analyzed antigen trafficking, dendritic cell (DC) activation, T cell responses, and gene expression via imaging, flow cytometry, and single-cell transcriptome sequencing.
• Assessed survival rates after pH1N1 virus challenge.

Main Results:

• Aged mice exhibited poorer antigen trafficking and DC activation, which PGA/Alum improved.
• PGA/Alum enhanced antigen-specific CD8+ T cell responses in aged mice to levels comparable to young mice.
• Single-cell analysis revealed PGA/Alum reduced inhibitory regulators in aged CD8+ T cells.
• Aged mice vaccinated with PGA/Alum-adjuvanted pH1N1 vaccine showed 100% survival against virus challenge, unlike unvaccinated aged mice (0% survival).

Conclusions:

• PGA/Alum significantly increases flu vaccine efficacy in aged mice.
• Enhanced efficacy is linked to improved DC activation and effector CD8+ T cell responses.
• PGA/Alum may represent a promising adjuvant for developing effective flu vaccines for the elderly population.