The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route

Edelman, Robert; Deming, Meagan E.; Toapanta, Franklin R.; Heuser, Mark D.; Chrisley, Lisa; Barnes, Robin S.; Wasserman, Steven S.; Blackwelder, William C.; Handwerger, Barry S.; Pasetti, Marcela; Siddiqui, Khan M.; Sztein, Marcelo B.

BACKGROUND: Reduced 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. RESULTS: Fifty-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. CONCLUSIONS: Our 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 REGISTRATION: ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered.