Introduction: Immunosenescence significantly reduces the efficacy of influenza vaccines in the elderly. This study explores the use of a clinically approved CpG 1018 adjuvant, an oligonucleotide-based adjuvant, to enhance influenza vaccine-induced immune responses to the influenza vaccine in aged mice, approximating the response in humans in their late 50s to early 60s.

Methods: Aged and young adult mice were immunized with the 2009 H1N1 pandemic influenza vaccine, with and without the CpG 1018 adjuvant. Serum antibody titers and cellular immune responses were evaluated. Mice were challenged with a lethal dose of mouse-adapted homologous viruses to evaluate the protective efficacy.

Results: In aged mice, CpG 1018 significantly increased influenza vaccine-induced serum antibody titers and Th1-biased CD4+ T cell responses and stimulated cytotoxic T lymphocytes. The CpG 1018-adjuvanted aged mice exhibited improved survival and reduced morbidity after the viral challenges as compared to those vaccinated without the adjuvant. In comparison, the non-adjuvanted vaccine induced more potent immune responses in the young adult mice.

Conclusions: Our data support the addition of CpG 1018 to influenza vaccines to enhance its immunogenicity and protective efficacy in aged mice. These findings advocate for the use of the CpG 1018 adjuvant in influenza vaccines for the elderly to enhance both humoral and cellular immune responses, thereby improving health outcomes in this vulnerable population.