Rescuing age-associated vaccine hyporesponsiveness in murine and nonhuman primate models with an immunostimulatory...

Age plays a crucial role in controlling the outcomes of infection, from duration and consequence to effectiveness of active immunization. Attenuated responses to vaccines in the elderly are contrary to the significant benefits that vaccination provides for society. The decline in normal immune function, collectively known as immunosenescence, is often reflected in reduced vaccine response rates. To investigate the influence of age on systemic immunization, different vaccine modalities in aged animals were compared to young counterparts, first in mice and then in nonhuman primates. In this work, reduced antibody production following systemic immunization was the major age-associated biomarker observed in aged mice and monkeys. The lower vaccine antibody phenotype observed in these aged animals was reversed using a well-established immunostimulatory adjuvant that has demonstrated clinical effectiveness in humans. This finding offers a valuable model for exploring age-related changes in the immune system that are associated with immunosenescence and importantly translatable solutions to address the associated outcomes for vaccines targeting the elderly population.