Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Aug;205(2):106-118.
doi: 10.1111/cei.13614. Epub 2021 Jun 8.

Therapeutic vaccination for treatment of chronic hepatitis B

Tamsin Cargill  1   2 , Eleanor Barnes  1   2   3
Affiliations
Review

Therapeutic vaccination for treatment of chronic hepatitis B

Tamsin Cargill et al. Clin Exp Immunol. 2021 Aug.

Abstract

Chronic hepatitis B infection remains a serious global health threat, contributing to a large number of deaths through liver cirrhosis and hepatocellular carcinoma. Current treatment does not eradicate disease, and therefore new treatments are urgently needed. In acute hepatitis B virus (HBV) a strong immune response is necessary to clear the virus, but in chronic infection the immune response is weakened and dysfunctional. Therapeutic vaccination describes the process of inoculating individuals with a non-infective form of viral antigen with the aim of inducing or boosting existing HBV-specific immune responses, resulting in sustained control of HBV infection. In this review we outline the rationale for therapeutic vaccination in chronic HBV infection, discuss previous and ongoing trials of novel HBV therapeutic vaccine candidates and outline strategies to improve vaccine efficacy going forward.

Keywords: T cell; hepatitis B; immunotherapy; vaccination.

PubMed Disclaimer

Conflict of interest statement

The authors have no financial conflicts of interest. Ellie Barnes is a named inventor and Ellie Barnes and Tamsin Cargill are contributors on a patent application describing ChAdOx1‐HBV vaccine reported in this manuscript (International Application no. PCT/GB2018/050948).

Figures

FIGURE 1
FIGURE 1
CD8 T cells are dysfunctional in chronic hepatitis B virus (HBV) infection. HBV undergoes replication in infected hepatocytes, which release HBV antigens including virions and secreted proteins. HBV‐specific T cells are repetitively stimulated by HBV antigen through their T cell receptor (TCR), which leads to the development of a molecular and transcriptional programme of T cell exhaustion, characterized by surface expression of check‐point inhibitors such as programmed cell death 1 (PD)‐1 and CD244 (2B4), mitochondrial dysfunction and transcription of TOX and Bim. As a result, HBV‐specific T cells become dysfunctional in cytokine secretion and proliferation, eventually undergoing apoptosis. HBV surface‐specific T cells are affected more severely than polymerase and core‐specific T cells. Figure created with BioRender
FIGURE 2
FIGURE 2
Strategies to improve therapeutic vaccination for chronic hepatitis B virus (HBV) infection. Strategies include (i) vaccinating individuals with lower HBV antigen loads or reducing antigenic load prior to vaccination with nucleos(t)ide therapy (NUCs), small inhibitory RNA (siRNA) or nucleic acid polymers (NAPs); (ii) reversing T cell dysfunction with concomitant treatment with check‐point inhibitors; (iii) optimization of vaccine immunogen by including multiple HBV antigens; (iv) combining vaccine platforms in heterologous prime‐boost strategies; and (v) targeting T cells to the liver via, for example, intravenous vaccination. Figure created with BioRender
See this image and copyright information in PMC

References

    1. World Health Organization . Global hepatitis report, 2017. https://www.who.int/hepatitis/publications/global‐hepatitis‐report2017/en/. Accessed 3 Oct 2019.
    1. World Health Organization (WHO) . Global health sector strategy on viral hepatitis 2016–2021. 2016. https://www.who.int/hepatitis/strategy2016‐2021/ghss‐hep/en/. Accessed 3 Oct 2019.
    1. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife. 2012;13:e00049. - PMC - PubMed
    1. Beasley RP, Trepo C, Stevens CE, Szmuness W. The e antigen and vertical transmission of hepatitis B surface antigen. Am J Epidemiol. 1977;105:94–8. - PubMed
    1. Chaudhuri AK, Follett EA, Burrell CJ. Anti‐e and vertical transmission of hepatitis B surface antigen. BMJ. 1977;2:1416–7. - PMC - PubMed

Publication types

MeSH terms

Substances