Recombinant vaccine development against Hepatitis B virus

Vaccination is a popular method of building up artificial immunity in our body against the pathogens that cause infectious diseases. In viral diseases, this is achieved by introducing antigens either as inactivated viruses or viral particles (epitopes) that are important in viral infectious mechanism, into the body to stimulate specific antibody production against the antigen

Often in recombinant vaccine production, gene that codes for a specific viral protein that acts as an antigen in our immune system (most probably a virus coat protein) is identified. Then, that gene is isolated from viral genome and cloned into a suitable expression vector under a specific promoter. Finally, the recombinant vector can be transformed into a suitable host to generate expected antigenic proteins in large amounts. Therefore, upon vaccination with these proteins prior to infection, will help to produce antibodies against the virus and they can be used against that virus in later infection (Figure 1).

Figure 1: Use of viral coat proteins in vaccines to stimulate antibody production upon real infection. Adopted from: Brown, T. Gene cloning and DNA analysis, 6th ed.; Wiley- blackwell; pp 252

Recombinant antiviral vaccine production involves several advantages over conventional vaccines. Such as, possible infections cause by presence of at least one active virus can be prevented, because recombinant vaccines contain only a part of the virus that can act as an antigen, whereas conventional vaccines involve inactivated whole viral particles. Therefore, these vaccines are known as non- infectious recombinant vaccines. Thus, most importantly recombinant vaccines can be produced in large scale, for some viruses such as Hepatitis B, as their growth is not supported by tissue culture media and therefore unable to produce conventional vaccines.

However, recombinant vaccines have been developed and approved by World Health Organization (WHO) against viruses including Hepatitis B. This virus can cause acute and chronic liver diseases and the most common form of transmission of this virus is prenatal transmission (from infected mother to her newborn child). This can be transferred to an healthy individual by exposure to infected blood or body fluids of an infected person as well. Acute infection of hepatitis B can cause several symptoms such as, jaundice, nausea, vomiting, abdominal pain etc. Sometimes, this acute infection can be detrimental if a liver failure occurs. Same fate is acquired if a chronic liver infection is developed. It can lead to serious situations like cirrhosis and liver cancer.

Hepatitis B viral DNA is covered by an outer lipoprotein coat with hepatitis B surface antigen (HBsAg) (Figure 2). This surface antigenic protein is coded by a gene called S gene in the viral genome. Isolation, cloning, transformation and expression of S gene produces antigenic hepatitis B surface proteins in large quantities, that can be used in vaccines. However, HBsAg can be found in two forms in the circulation of an infected person. One form of HBsAg is found on viral coat while, the other form circulates freely in the blood. This free form of HBsAg is arranged into 22nm sphere and are known to be the predominant form in the blood upon infection. Therefore, use of HBsAg proteins produce more antibodies upon vaccination, when compared with using HBcAg and HBeAg that are found in viral core.

Figure 2: Hepatitis B vius.Adopted from: Gitlin, N. Hepatitis B: Diagnosis, Prevention, And Treatment. Clinical Chemistry 1997, 43 (8), 1500-1506.

Although, several treatment strategies such as, adaptive immune transfer, use of interferons, immunomodulators and nucleoside analogs are available for hepatitis B infection, non- infectious recombinant hepatitis B vaccine has proven to be more effective against the virus.

Author: Thaanya Amarasekara
B.Sc. (Honors degree in Biochemistry and Molecular Biology)
Undergraduate
Faculty of Science
University of Colombo

References:

1) Gitlin, N. Hepatitis B: Diagnosis, Prevention, And Treatment. Clinical Chemistry 1997, 43 (8), 1500-1506.
(2) Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b (accessed Jul 6, 2020).
(3) Brown, T. Gene cloning and DNA analysis, 6th ed.; Wiley- blackwell; pp 252- 253.