CD25⁺ cell depletion enhances protective immunity of PR8 inactivated influenza vaccine in aged mice

Immunosenescence is a real biological process that leads to a quantitatively and qualitatively weaker immune response to vaccines in the aged population. The adaptive immune system, especially B cells and T cells, is responsible for creating targeted, long-lasting immune memory and is the component most directly responsible for vaccine efficacy. However, this system undergoes substantial functional decline with aging. This study evaluated whether depletion CD25⁺ cell in combination with a saponin-based ISCOMs adjuvant enhances the efficacy of PR8 inactivated influenza vaccine in aged mice. Aged BALB/c mice were depleted of CD25⁺ cells using an anti-CD25 monoclonal antibody prior to intramuscular vaccination with inactivated PR8 virus, either with or without the ISCOMs adjuvant. The combination of CD25⁺ depletion and the adjuvant induced robust antibody responses, promoted a balanced IgG2a/IgG1 ratio, significantly elevated hemagglutination inhibition titers, markedly reduced lung viral loads, and provided complete protection against a lethal challenge. These results demonstrate that targeting CD25 signaling in combination with a saponin-based adjuvant offers a promising strategy to overcome immunosenescence and enhance influenza vaccine efficacy in the elderly.