Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
RECOMBINANT-DERIVED HEPATITIS B VACCINE: A PARADIGM FOR OTHER SUBUNIT VACCINES
AIDS Vaccine Research and Clinical Trials. Putney SD and Bolognesi DP, eds. New York, Marcel Dekker, p. 381-407, 1990.. Unique Identifier : AIDSLINE ICDB/91676957 Ellis RW; Dept. of Cellular and Molecular Biology, Merck Sharp and Dohme; Res. Lab., West Point, PA
Abstract:
The yeast-derived hepatitis B vaccine is the first recombinant-derived vaccine approved for human use. It serves as a paradigm for the development of future recombinant subunit vaccines. The molecular biology and expression system, preclinical biological analysis of vaccine antigen, and clinical testing of this virus are reviewed. To produce a recombinant hepatitis B vaccine, it was necessary to insert the hepatitis B surface antigen (HBsAg) gene into an expression vector capable of directing the synthesis of large quantities of HBsAg in a heterologous host cell. Satisfactory levels of expression were achieved in the yeast Saccharomyces cerevisiae. Recombinant yeast cells expressing HBsAg are grown in tank fermentors, inoculated from stored vials of a stable production master seed. The antigen can be purified from lysed cells to greater than 99% purity. Efficacy in chimpanzees is the most important preclinical immunologic test. Vaccinated animals produced anti-HBs titers of 800-3000 mIU/ml. After challenge with HBV, none of the vaccinated animals showed any signs of viral infection throughout the entire observation period. In studies in infants born to chronic carrier mothers, a 94% rate of protection was demonstrated using the yeast-derived vaccine. This was comparable with the rate obtained in a control group receiving plasma-derived vaccine. (Both groups also received passive immunization at birth with one dose of hepatitis B immune globulin) The successful development of the yeast-derived HBV vaccine serves as a model for future recombinant-derived subunit vaccines. Major issues for the development program for HBsAg included choice of host cell, expression system, master seed, culture scale-up, purification, preclinical analysis, and clinical evaluation. These issues deserve consideration with respect to a potential subunit AIDS vaccine, but it is impossible to apply these considerations due to a lack of understanding of HIV to a point where an actual candidate AIDS vaccine antigen can be identified. All issues regarding expression, seed development, and culture scale-up are similar to those for the HBV vaccine. Most of the technical tools are available for producing a subunit AIDS vaccine, but it is unclear at present which polypeptides should be included in such a vaccine as a candidate antigen. (65 Refs)
Keywords: Acquired Immunodeficiency Syndrome/IMMUNOLOGY/PREVENTION & CONTROL Animal Chimpansee troglodytes Hepatitis B/PREVENTION & CONTROL Hepatitis B Surface Antigens/IMMUNOLOGY Hepatitis B Virus/*IMMUNOLOGY Human HIV/IMMUNOLOGY HIV Antigens/IMMUNOLOGY Vaccines, Synthetic/ADMINISTRATION & DOSAGE/*IMMUNOLOGY Viral Hepatitis Vaccines/ADMINISTRATION & DOSAGE/*IMMUNOLOGY Viral Vaccines/ADMINISTRATION & DOSAGE MONOGRAPH REVIEW 912130
M91C4085
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
