Immune senescence in old and very old rhesus monkeys: reduced antibody response to influenza vaccination

Abstract

The health of old monkeys usually begins to deteriorate by 20 years of age, coinciding with the onset of a slowly progressing immune senescence. Changes in lymphocyte subsets and responses to several antigens have been characterized in geriatric primates, but systematic research has not been conducted on vaccination against influenza virus, a topic of considerable clinical concern for elderly humans. Antibody responses were significantly reduced to primary immunizations in old monkeys, but by administering a second vaccine at 1 month, it was possible to boost antibody titers up to the level found in young adults during their primary phase. The immune competence of unusually long-lived animals (26-37 years) was also compared to more typical aged monkeys (19-25 years). Antibody responses were low overall, although some monkeys in both age groups did respond to immunization. Among the oldest animals, the leukocytes of the responders with higher antibody titers were found to release more interleukin-2 following in vitro stimulation with an anti-CD3/anti-CD28 cocktail relative to their cellular reactions to staphylococcal enterotoxin B. The general decline in immune vigor, and the marked individual variation in how old monkeys age, provides a useful animal model for investigating factors associated with immunosenescence.

Fig. 1

Primary and secondary antibody responses of 31 young adult and eight old rhesus monkeys to vaccination. The antibody responses of old monkeys were significantly reduced, but a booster immunization raised their secondary titers into the primary range for young adults. A relative scale is portrayed using area under the curve (AUC) based on computations of antibody titer from three serial dilutions of sera. Vertical arrows indicate when the two trivalent vaccines were administered

Fig. 2

Primary antibody responses of eight old and 14 very old rhesus monkeys to influenza vaccination. Antibody levels were low overall and significantly lower in the oldest animals, although responders were found in both age groups. Note that the scale for minimal responders is expanded (2x) to illustrate their low responses. Responder status was based on attaining an AUC >100, a criterion generated from the young adult monkeys in study 1. Circles illustrate data for the old monkeys; triangles connote the older ones. Mean responses for the group are shown with bold lines and larger symbols; lighter lines indicate individual responses. Additional information on these monkeys is provided in Table 1