Abstract
BackgroundReduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions.ResultsFifty-two healthy, community dwelling elderly adults (65–82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21–34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly.ConclusionsOur data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations.Clinical trial registrationClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered.
Highlights
Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation
This phenomenon is ascribed to age-related alterations of the immune system, or immunesenescence, which is caused by multiple factors including deficits in T cell proliferation, signaling, and activation, in T cell help to B cells, in expression of Toll-like receptors (TLRs) and antigen presentation, as well as waning of naïve B and T cell populations [3,4,5,6,7]
Divergent immune responses to vaccination in elderly individuals are often complicated by the comorbid or confounding conditions that accompany aging
Summary
Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. Vaccines remain a powerful tool for the prevention of infectious diseases in the elderly, but older adults respond less vigorously to vaccinations (e.g., influenza, pneumococcal pneumonia, zoster, and Hepatitis B) when compared to younger individuals [1, 2] This phenomenon is ascribed to age-related alterations of the immune system, or immunesenescence, which is caused by multiple factors including deficits in T cell proliferation, signaling, and activation, in T cell help to B cells, in expression of Toll-like receptors (TLRs) and antigen presentation, as well as waning of naïve B and T cell populations [3,4,5,6,7]. Despite the lower protection rates following primary vaccination for HBV, booster responses for older adults (> 65 years) after re-vaccination (for individuals with documented vaccination > 10 years prior) appear to be intact in elderly, suggesting that the ability of T cells to generate lasting memory following a di novo vaccination declines with age [14]
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