Preexisting Immunity, More Than Aging, Influences Influenza Vaccine Responses

Seasonal influenza is responsible for an estimated 23 000 deaths (range, 3349–48 614) annually in the United States [1, 2]. The majority of these deaths occur among adults aged 65 years and older [1]. Adults age 65+ have 10 to 30 times more hospitalizations annually due to influenza-associated illness than younger adults and longer hospital stays [2–6]; these effects are even more pronounced with more advanced age [2]. Although vaccination remains the most cost-effective method to reduce influenza-associated morbidity and mortality, immunosenescence renders vaccines less effective in older adults [7, 8]. Contributing factors include impaired T and B cell functionality and narrowing of the T and B cell repertoire [9–15]. Although it is recognized that more effective vaccines are needed for older adults, the capacity of their immune systems to respond and the components of the immune system that should be targeted for improved efficacy are not well understood. The hemagglutination inhibition (HI) assay is currently used to evaluate vaccine immunogenicity, in part because an HI antibody titer ≥32 or 40 is generally considered a laboratory correlate of protection, having been associated with protection against influenza infection in 50% of the population in a number of studies in younger adults [16–19]. Findings from recent studies also suggest that cell-mediated immune responses may correlate better with protection in older individuals [20, 21]. However, alternative correlates to HI have not yet been established. Although multiple studies have compared immune responses of older adults to young healthy adults, relatively fewer have examined the progression in later life. This study examines factors influencing immune responses to seasonal trivalent inactivated influenza vaccine (TIV) progressing from middle-age (age 50–59 years) through advanced age (age 80+) using a comprehensive set of assessments for antibody and cell-mediated immune responses.