# Dissecting Hepatitis B Vaccine Adjuvant Effects on Immune Responses and the HIV Reservoir in PLWH

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $744,728

## Abstract

Project Summary
Hepatitis B virus (HBV) is a leading cause of cirrhosis and liver cancer globally, resulting in over 800,000
deaths annually. Approximately 10% of people living with HIV (PLWH) worldwide are infected with HBV and
prevention of HBV infection remains a critical goal in PLWH. Vaccination with ENGERIX-B and other alum
adjuvanted hepatitis B surface antigen (HBsAg) vaccines has been the cornerstone of HBV prevention, but the
response to current standard vaccination is suboptimal in PLWH. HEPLISAV-B vaccine is HBsAg combined
with CpG 1018 adjuvant, a Toll-like receptor 9 (TLR9) agonist. A Phase III trial, A5379, randomized PLWH
with a prior history of HBV vaccination who do not achieve protective HBsAb levels to receive three doses of
HEPLISAV-B or ENGERIX-B. Preliminary analysis demonstrates significantly higher response rates with
HEPLISAV-B. To explore the immunologic mechanisms associated with increased rates of response, we plan
to compare innate and adaptive immune responses induced by HEPLISAV-B to those of ENGERIX-B
vaccination. In Aim 1, we define the innate immune signatures of CpG 1018 and alum adjuvated HBsAg
vaccination, including plasma chemokine and cytokine and transcriptomic profiles that are associated with
response to vaccination and with adaptive cell phenotypes defined in Aim 2. In Aim 2, we compare HBsAg-
specific B- and T-cell responses following three doses of HEPLISAV-B to those induced with a standard three-
dose regimen of ENGERIX-B, using high dimensional flow cytometry and single cell RNAseq to define the
immunologic and metabolic profiles of HBV-specific T and B cells associated with vaccine response. Previous
studies have shown that TLR9 activation in HIV infection increases HIV-1 transcription and reduces proviral
DNA, key outcomes in HIV-1 cure strategies. Thus, Aim 3 will assess the HIV reservoir and HIV-specific
immune responses before and after vaccination with HEPLISAV-B. With these three complementary but
independent aims, we will define innate and cellular characteristics associated with superior antibody
production, with broad implications regarding the use of TLR9 agonist vaccine adjuvants in populations with
suboptimal vaccine responses and improved understanding of dysregulation of immune responses in PLWH.
Additionally, this research leverages a large and diverse participant group to explore the dynamics of HIV
reservoir maintenance after TLR9 agonist exposure with the potential to inform development of HIV curative
strategies.

## Key facts

- **NIH application ID:** 11007747
- **Project number:** 1R01AI186730-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ANDREA L COX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $744,728
- **Award type:** 1
- **Project period:** 2024-07-25 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11007747

## Citation

> US National Institutes of Health, RePORTER application 11007747, Dissecting Hepatitis B Vaccine Adjuvant Effects on Immune Responses and the HIV Reservoir in PLWH (1R01AI186730-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11007747. Licensed CC0.

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