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Original Article

Subunit, Recombinant and Synthetic Hepatitis B Vaccines

Pages 27-38 | Published online: 08 Jul 2009
 

Abstract

Hepatitis B surface antigen in the form of 22 nm spherical particles (and tubular forms) is excess virus coat protein. Guidelines for the preparation of the 22 nm spherical particles (and their separated polypeptides) derived from the plasma of asymptomatic human carriers, were suggested by the WHO Expert Committee on Viral Hepatitis in 1977, and the proposed requirements for the 22 nm hepatitis B particle vaccine were published by the WHO Expert Committee on Biological Standardisation in 1981 and revised in 1983. Such preparations have been tested for safety and protective efficacy and many clinical trials with the plasma-derived vaccine have demonstrated the immunogenicity, high protective efficacy and safety of the currently licensed preparations.

Polypeptide vaccines, derived from the surface antigen from any source. have several advantages which include precise biochemical characterisation. exclusion of genetic material of viral origin. exclusion of host or donor-derived substances and enhanced potency. A polypeptide vaccine in micellar form has been developed in London.

The applications of recombinant DNA technology permit the isolation, purification and selective amplification of almost any individual segment of DNA from practically any organism in convenient biological systems such as bacteria, yeast. or any other cell including mammalian cells. Considerable progress has been made with vaccines prepared from antigen expressed in yeast (Saccharomyces cerevisiae). Cloning of the DNA of hepatitis B virus has resulted in sequencing of nucleotides and mapping of the amino acids of antigens. Information obtained from the sequencing of the 226 amino acids of hepatitis B surface antigen has led to the development of chemically synthesised peptides corresponding to amino acid sequences predicted from the nucleotide map. Several such synthetic peptides. when linked to potent adjuvants elicit antibodies in experimental animals which react with the surface antigen. the potential of pure chemically synthetic vaccines against hepatitis B, and other infectious agents, is under intensive investigation since such vaccines should be chemically well-defined, uniform, safe and cheap to produce.

Studies have been carried out recently using a chemically synthetic peptide in a linear and in a cyclical form corresponding to the amino acids sequence 139–147 of the major polypeptide I of hepatitis B surface antigen. the synthetic antigens and the native polypeptide complex p23-gp28 purified from hepatitis B surface antigen in plasma were used for the measurement of affinity of the antibody to the surface antigen (anti-HBs) in human sera. the levels and affinity of anti-HBs produced by healthy persons after immunisation with the licensed plasma-derived hepatitis B vaccine were studied using three antigens. the results showed that the antibody affinity increased progressively throughout the period of immunisation but the pattern of affinity maturation varied according to the peptide used as an antigen. the majority of individuals showed a significant rise in antibody affinity after the third (booster) dose of vaccine given at six months. the use of chemically synthetic peptides thus allows for the first time a quantitative and qualititative assessment of antibody responses to hepatitis B vaccine. These studies also confirmed that selected peptides corresponding to relevant epitopes of hepatitis B surface antigen may be useful as synthetic hepatitis B vaccines.

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