Heplisav-B Revaccination for Hepatitis B Vaccine Nonresponders

HIV-positive individuals are at increased risk of morbidity and mortality from Hepatitis B co-infection, due to shared routes of transmission, increased likelihood of developing chronic infection (as opposed to spontaneous clearance), and increased immune dysregulation leading to accelerated disease progression, and so current guidelines recommend the routine vaccination of HIV-positive individuals against HBV. However, because achieved seroprotection rates (SPR) are historically lower than in HIV-negative individuals, post-vaccination serologic testing is recommended for this group and re-vaccination (with increased dose or additional doses) should be attempted for those who were non-responders to the initial vaccine. Heplisav-B is a HBV vaccine adjuvanted with a TLR9 agonist that has shown improved SPR among groups with reduced response rates to classic alum-adjuvanted vaccines, such as those with CKD, obesity, or diabetes. The investigators propose to evaluate immunological mechanisms of protection in Veterans who were non-responders to prior HBV vaccination now receiving Heplisav vaccinations. The investigators will enroll a comparison group of HIV-negative individuals to characterize the HIV-associated immune alterations that modulate vaccine response. The investigators hypothesize that TLR9-mediated innate immune stimulation with Heplisav will elicit HBV seroprotection despite prior vaccination failures in persons living with HIV, compared to HIV uninfected individuals. By assessing innate immune responses and B cell immunophenotypes at baseline, post-vaccination, and at long-term followup in Veterans with and without HIV the investigators will assess the mechanisms by which the immunostimulatory effects of TLR9 agonists may overcome the immune dysfunction in these patients.