Heplisav-B Revaccination for Hepatitis B Vaccine Nonresponders
Condition: HIV Infections; Hepatitis B; Vaccine Response Impaired
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Study type: Observational

Summary: 
      The goal of this natural history study is to examine the immune responses to the Heplisav-B
      vaccine in Veterans living with HIV who were non-responders to prior HBV vaccination. A
      comparison group of HBV vaccine nonresponders without HIV infection will be enrolled to
      characterize the HIV-associated immune alterations that affect 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.

      Participants eligible for Heplisav-B vaccination will be asked to provide blood samples at
      multiple timepoints before and after their vaccination.
    

Detailed description: 
      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.
    

Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The target population includes patients (or healthcare providers) who have received prior
        Hepatitis B vaccines without achieving seroprotection (defined as a negative SAb
        qualitative titer or a SAb quantitative titer <10 mIU/mL collected at least 30 days after
        last vaccine dose). The primary enrollment group will include Veterans living with HIV,
        with a comparator group of HIV-negative individuals. An additional exploratory population
        of HBV vaccine nonresponders who were successfully treated for HCV infection may be
        included to provide an opportunity for evaluation of the immune responses in patients who
        have been cured of chronic viral infections.
      
Keywords: Heplisav-B; HIV; vaccine