Development of Therapeutic Vaccine for Chronic Hepatitis B: Concept, Cellular and Molecular Events, Design, Limitation, and Future Projection

Abstract

Four decades have passed since the first usage of the therapeutic vaccine in patients with chronic hepatitis B (CHB). However, there is no approved regimen of vaccine therapy for the treatment of CHB. This is mainly attributable to faulty conception, an improper understanding of the cellular and molecular mechanisms of CHB, and the impaired design of vaccine therapy for CHB. With the advent of new techniques and a better understanding of cellular and molecular mechanisms underlying the genesis of CHB, the limitations and failures of previous regimens of therapeutic vaccines have been primarily understood. Additionally, the importance of immune therapy for treating millions of CHB patients and achieving the target of "Elimination of Hepatitis by 2030" has been focused on in the international arena. This has been amplified by the apparent limitation of commercially available antiviral drugs that are infinite in duration, endowed with safety concerns, and unable to cure liver damage due to their minimal immune modulation capacities. The proposed review article comprehensively discusses each of these points and proposes evidence-based approaches for viable types of vaccine therapy for the treatment of CHB.

Keywords: chronic hepatitis B; molecular mechanisms; scope and limitation; vaccine therapy.

Figure 1

Spectrum of HBV infection in the world and targets of the World Health Organization to achieve “Elimination of Hepatitis by 2030” [8,9]. HBV, hepatitis B virus; CHB, chronic hepatitis B; HBsAg, hepatitis B surface antigen; ALT, alanine aminotransferase; WHO; World Health Organization.