Timeline of key events related to hepatitis B

1972-12-01T00:00:00+00001975-01-01T00:00:00+0000AU Bertland, AA Tytell, GP Lampson, E Buynak, 'Method for purifying hepatitis B antigen'm US Patent US4017360A. The patent was granted 12 April 1977.1975-05-14T00:00:00+0000WJ McAleer, EH Wamuth, 'Process for isolating hepatitis b antigen', US Patent 4024243. The patent was granted 17 May 1977.1975-06-16T00:00:00+0000The study carried out in 12 chimpanzees indicated the vaccine would be safe to test in humans, MR Hilleman, EB Buynak, RR Roehm, AA Tytell, AU Bertland, 'Purified and inactivated hepatitis vaccine: Progress Report', American Journal of Medical Sciences, 279/2 (1975), 401-4.1975-09-01T00:00:00+0000Conducted among 1,083 gay men in New York. Gay men were ten times more likely to get hepatitis B than the normal population. Men injected with the vaccine were found to be 75% less likely to get hepatitis B than those who didn't get the vaccine. The trial was done by Wolf Szmuness at New York Medical Center using the vaccine produced by Hilleman at Merck. 1978-01-01T00:00:00+0000The vaccine was developed by Alfred Prince in partnership with John Vnek. Together they devised easier and less expensive purification steps than those used by Merck. The new vaccine required a tenth of the dose than Merck's vaccine. All these measures helped reduce the cost of the vaccine, which was 50 cents per dose. This compared with $90 to $100 for 3 doses of the Merck plasma vaccine. The low cost vaccine was licensed to Cheil Division of Samsung, Korea, Wuhan Institute in China and the Ministry of Healthy in Burma. 1978-01-01T00:00:00+0000The patent was filed on the basis of work undertaken by Kenneth Murray. 1978-12-22T00:00:00+0000The work, funded by Biogen, was undertaken as part of a project to develop recombinant hepatitis B vaccine. It was published in CJ Burrell, P Mackay, PJ Greenaway, PH Hofsneider, K Murray, 'Expression in Escheria Coli of hepatitis B virus DNA sequences cloned in plasmid pBR322', Nature, 279/5708 (1979), 43-47. 1979-02-01T00:00:00+0000F Galibert, E Mandart, F Fitoussi, P Tiollais, P Charnay, , 'Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature, 281/5733 (1979), 646-50; P. Charnay, C Pourcel, A Louise, A Fritsch, P Tiollais, 'Cloning in Escherichia coli and physical structure of hepatitis B virion DNA', PNAS USA, 76/5 (1979), 2222-26; P Charnay, E Mandart, A Hampe, F Fitoussi, P Tiollais, F Galibert, 'Localization on the viral genome and nucleotide sequence of the gene coding for the two major polypeptides of the hepatitis B surface antigen (HBs Ag)', Nucleic Acids Research, 7/2 (1979), 335-46.1979-05-01T00:00:00+0000The research was funded by Merck with the aim of developing a recombinant vaccine against hepatitis B. It was published in P Valenzuela, P Gray, M Quiroga, J Zaldivar, H M Goodman, WJ Rutter, 'Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen', Nature, 280/5725 (1979), 815e819.1979-08-30T00:00:00+0000The patent was based on the work of Kenneth Murray. It was granted in July 1990 as European Patent (UK) No 0182442. 1979-12-21T00:00:00+00001980-01-01T00:00:00+0000JC Edman, P Gray, P Valenzuela, LB Rall, WJ Rutter, 'Integration of hepatitis B virus sequences and their expression in a human hepatoma cell', Nature, 286/5772 (1980), 535-38.1980-07-31T00:00:00+00001981-01-01T00:00:00+00001981-07-01T00:00:00+0000The vaccines were made with HBsAg purified from plasma of people with chronic hepatitis B. The vaccines were Hevac B Pasteur - made by Merieux and the Pasteur Institute and Hepatavax made by Maurice Hilleman at Merck.1982-01-01T00:00:00+0000The programme, called the Hepatitis B eradication 5-year programme, used plasma-derived vaccines developed by Korean companies: Korean Green Cross, Cheil, and LG Industry. 1982-01-01T00:00:00+0000WHO, WHO Technical Report Series, No. 691 (Geneva: WHO, 1983).1983-01-01T00:00:00+0000The trial was done with 37 healthy adult volunteers. The vaccine was made using HBsAg cloned in yeast. EM Scolnick, AA McLean, DJ West, WJ McAleer WJ Miller, EB Buynak, 'Clinical evaluation in healthy adults of a hepatitis B vaccine made by recombinant DNA', JAMA 251/21 (1984), 2812-15. 1984-06-01T00:00:00+0000
Date Event People Places Sciences
December 1972UK introduced testing to screen for HBsAg for all blood donations   
1975Pasteur Institute scientists started to develop fractionation method to purify HBsAg from plasma to produce hepatitis B vaccineTiollaisPasteur InstituteVaccines
14 May 1975Merck filed US patent for technique to purify hepatitis B antigenBertland, Tytell, Lampson, BuynakMerckVaccines, Infectious diseases
16 Jun 1975Merck filed US patent for process to isolate hepatitis B antigenMcAleer, WasmuthMerckVaccines, Infectious diseases
September 1975Merck reported positive results from chimpanzee trials with hepatitis B vaccine containing inactivated HBsAg antigenHilleman, Buynak, Roehm, Tytell, BertlandMerckVaccines, Infectious diseases
1978 - 1980First clinical trials with plasma vaccine against hepatitis BSzmuness, HillemanNew York Medical CenterVaccines, Infectious diseases
1978 - 1986Low-cost plasma hepatitis B vaccine developedPrince, VnekNew York Blood CenterVaccines
December 1978Biogen filed preliminary UK patent for technique to clone hepatitis B DNA and antigensKenneth MurrayBiogen, University of EdinburghRecombinant DNA, Vaccines, Infectious diseases
February 1979University of Edinburgh scientists published the successful isolation and cloning DNA fragments of the hepatitis B virus in Escherichia coliBurrell, Mackay, Greenaway, Hofschneider, K MurrayUniversity of Edinburgh, Microbiological Research Establishment, BiogenRecombinant DNA, Vaccine
May 1979 - Oct 1979Pasteur Institute scientists reported successful cloning of hepatitis B DNA in Escherichia coliGalibert, Mandart, Fitoussi, Tiollais, Charnay, HampePasteur InstituteRecombinant DNA, Vaccines, Infectious diseases
30 Aug 1979UCSF scientists announced the successful cloning and expression of HBsAg in Escherichia coliValenzuela, Gray, Quiroga, Zaldivar, Goodman, RutterUniversity of California San Francisco, MerckRecombinant DNA, Vaccines, Infectious diseases
21 Dec 1979Biogen applied for European patent to clone fragment of DNA displaying hepatitis B antigen specificityMurrayBiogenRecombinant DNA, Vaccines, Infectious diseases
1980Pasteur Institute filed for US patent for fractionation method to purify HBsAg from plasma to produce hepatitis B vaccineTiollaisPasteur InstituteVaccines, Infectious diseases
31 Jul 1980UCSF scientists published method to culture HBsAg antigens in cancer cellsEdman, Gray, Valenzuela, Rall, RutterUniversity of California San FranciscoVaccine, Recombinant DNA
1981 - 1991US hepatitis B vaccination programme directed towards people identified at high risk  Vaccine
July 1981UCSF and Merck filed patent to snthesise HBsAg in recombinant yeastRutterUniversity of California San Francisco, MerckVaccine, Recombinant DNA
1982First plasma vaccines against hepatitis B licensed for market in US and EuropeHillemanMerieux, Institute Pasteur, MerckVaccines, Infectious diseases
1982South Korea government launched nationwide hepatitis B immunisation programme   Vaccines
1983WHO argued hepatitis B virus second only to tobacco as cause of cancer  Oncology, Virology
1 Jun 1984Genetically engineered vaccine against hepatitis B reported to have positive trial resultsScolnick, McLean, West, McAleer , Miller, BuynakMerck, University California San FranciscoRecombinant DNA, Vaccines, Infectious diseases

Dec 1972

UK introduced testing to screen for HBsAg for all blood donations

1975

Pasteur Institute scientists started to develop fractionation method to purify HBsAg from plasma to produce hepatitis B vaccine

14 May 1975

Merck filed US patent for technique to purify hepatitis B antigen

16 Jun 1975

Merck filed US patent for process to isolate hepatitis B antigen

Sep 1975

Merck reported positive results from chimpanzee trials with hepatitis B vaccine containing inactivated HBsAg antigen

1978 - 1980

First clinical trials with plasma vaccine against hepatitis B

1978 - 1986

Low-cost plasma hepatitis B vaccine developed

Dec 1978

Biogen filed preliminary UK patent for technique to clone hepatitis B DNA and antigens

Feb 1979

University of Edinburgh scientists published the successful isolation and cloning DNA fragments of the hepatitis B virus in Escherichia coli

May 1979 - Oct 1979

Pasteur Institute scientists reported successful cloning of hepatitis B DNA in Escherichia coli

30 Aug 1979

UCSF scientists announced the successful cloning and expression of HBsAg in Escherichia coli

21 Dec 1979

Biogen applied for European patent to clone fragment of DNA displaying hepatitis B antigen specificity

1980

Pasteur Institute filed for US patent for fractionation method to purify HBsAg from plasma to produce hepatitis B vaccine

31 Jul 1980

UCSF scientists published method to culture HBsAg antigens in cancer cells

1981 - 1991

US hepatitis B vaccination programme directed towards people identified at high risk

Jul 1981

UCSF and Merck filed patent to snthesise HBsAg in recombinant yeast

1982

First plasma vaccines against hepatitis B licensed for market in US and Europe

1982

South Korea government launched nationwide hepatitis B immunisation programme

1983

WHO argued hepatitis B virus second only to tobacco as cause of cancer

1 Jun 1984

Genetically engineered vaccine against hepatitis B reported to have positive trial results

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