Heplisav-B Revaccination for Hepatitis B Vaccine Nonresponders

HIV Infections Clinical Trial

— HBR2  

Official title:

Heplisav-B Revaccination for Hepatitis B Vaccine Nonresponders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05791851
• Other study ID #: HP-83378
• Status: Completed
• Start date: October 23, 2019
• Est. completion date: June 14, 2022

Study information

• Verified date: March 2023
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 14, 2022
• Est. primary completion date: June 14, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 109 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• HIV Infections
• Vaccine Response Impaired

Locations

Country	Name	City	State
United States	Baltimore Veterans Affairs Medical Center	Baltimore	Maryland
United States	Institute of Human Virology	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	Baltimore Veterans Affairs Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in B cell functional responses	Characterize the change in B cell functional responses by ELISpot on day 30 compared to baseline	Day 30
Primary	Change in B cell functional responses	Characterize the change in B cell functional responses by ELISpot on day 60 compared to baseline	Day 60
Primary	Change in B cell functional responses	Characterize the change in B cell functional responses by ELISpot on day 365 compared to baseline	Day 365
Primary	Change in B cell phenotypic responses	Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline	Day 30
Primary	Change in B cell phenotypic responses	Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline	Day 60
Primary	Change in B cell phenotypic responses	Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline	Day 365
Primary	Cytokine profile	Change in cytokine profile on day 1 compared to baseline	Day 1
Secondary	Hepatitis B surface antibody responses	Characterization of the hepatitis B surface antibody titers on day 30 compared to baseline	Day 30
Secondary	Hepatitis B surface antibody responses	Characterization of the hepatitis B surface antibody titers on day 60 compared to baseline	Day 60
Secondary	Hepatitis B surface antibody responses	Characterization of the hepatitis B surface antibody titers on day 365 compared to baseline	Day 365
Secondary	Hepatitis B surface antibody response rates	Characterization of the hepatitis B surface antibody response rates on day 30 compared to baseline	Day 30
Secondary	Hepatitis B surface antibody response rates	Characterization of the hepatitis B surface antibody response rates on day 60 compared to baseline	Day 60
Secondary	Hepatitis B surface antibody response rates	Characterization of the hepatitis B surface antibody response rates on day 365 compared to baseline	Day 365