Clinical trial NCT05791851: Heplisav-B Revaccination for Hepatitis B Vaccine Nonresponders
Official title: Heplisav-B Revaccination for Hepatitis B Vaccine Nonresponders
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Hepatitis B
Vaccine Response Impaired
Keywords: Heplisav-B
HIV
vaccine
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Baltimore VA Medical Center
First posted: 2023-03-30
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 109
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
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.

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Age \>18 by age of screening
* If HIV positive, either:

  * Suppressed on a stable, ARV regimen for \>4 weeks with CD4 count \>100. HIV VL suppressed \<50 copies/mL, although single isolated VL \>50 not excluded.

OR

* Untreated ≥ 8 weeks with CD4 count \>100

  * Prior HBV vaccine (other than Heplisav) with last dose \>30 days prior to screening and anti-HBSAg ≤10 IU/mL measured \>30days from last vaccine dose. (No exclusion for HBV CAb positive.)
  * Ability to provide informed consent and adhere to clinic visits (in the judgment of both the participant and the provider)
  * No history of adverse reaction to HBV vaccines or components thereof
  * If HCV Ab positive: undetectable HCV viral load and \>12 weeks from completion of any HCV therapy.

Exclusion Criteria:

* History of allergic reaction to HBV vaccines or components (including yeast)
* HBsAb titer \>10 IU/mL on screening evaluation
* Clinically significant illness (other than HIV) that may, in the opinion of the investigator, interfere with the subject treatment, or adherence to protocol. This may include but is not limited to a history of transplant, decompensated cirrhosis, or malignancy that may interfere with host immunity.
* Poor venous access interfering with blood sample collection
* Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.
* No exclusion will be made for chronic renal disease or ESRD

Primary outcomes:
measure: Change in B cell functional responses
timeFrame: Day 30
measure: Change in B cell functional responses
timeFrame: Day 60
measure: Change in B cell functional responses
timeFrame: Day 365
measure: Change in B cell phenotypic responses
timeFrame: Day 30
measure: Change in B cell phenotypic responses
timeFrame: Day 60
measure: Change in B cell phenotypic responses
timeFrame: Day 365
measure: Cytokine profile
timeFrame: Day 1
Secondary outcomes:
measure: Hepatitis B surface antibody responses
timeFrame: Day 30
measure: Hepatitis B surface antibody responses
timeFrame: Day 60
measure: Hepatitis B surface antibody responses
timeFrame: Day 365
measure: Hepatitis B surface antibody response rates
timeFrame: Day 30
measure: Hepatitis B surface antibody response rates
timeFrame: Day 60
measure: Hepatitis B surface antibody response rates
timeFrame: Day 365
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Baltimore Veterans Affairs Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Institute of Human Virology
state: Maryland
Study officials:
References: