Vaccine: Timeline of key events

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The 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+0000The vaccine was developed by Stanley Plotkin, Hilary Koprowski and Tadeusz Wiktor at the Wistar Institute1980-01-01T00:00:00+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 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+00001984-07-01T00:00:00+0000An American microbiologist, Enders shared the 1954 Nobel Prize for helping to develop a technique to grow the poliomyeltitis virus in various types of tissue culture. This he achieved with colleagues Thomas Weller and Fredric Robbins in 1949. Their technique paved the way for Jonas Salk's development of a vaccine against polio. Enders is also renowned for having helped pioneer the first measles vaccine. 1985-09-08T00:00:00+0000The vaccine, Hepatabox, was developed by Green Cross using Prince and Vnek's technique. 1986-01-01T00:00:00+0000The vaccine was first approved in West Germany, in May, and then in the US in July. The vaccine was regarded as a breakthrough because it was made from a genetically engineered sub-particle of the virus. This made it much safer than the original vaccine which used the virus sub-particle sourced from the blood of hepatitis B sufferers. The vaccine heralded a new era for the production of vaccines and is a major weapon against one of the most infectious diseases. 1986-05-01T00:00:00+0000HepataxinB was developed by Cheil Sugar using the technique licensed from Alfred Prince and John Vnek.1986-11-01T00:00:00+00001986-12-01T00:00:00+0000The technology was developed at Merck's plant in Montgomery County, Philadelphia. The deal was initiated by Roy Vagelos, Merck's CEO. The aim was to help China deal with its major hepatitis B problem.1989-01-01T00:00:00+00001989-01-01T00:00:00+00001989-05-01T00:00:00+00001990-01-01T00:00:00+00001993-01-01T00:00:00+0000
Date Event People Places Sciences
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, Vaccine
21 Dec 1979Biogen applied for European patent to clone fragment of DNA displaying hepatitis B antigen specificityMurrayBiogenRecombinant DNA, Vaccine
1980US licensed first rabies vaccine for human useKoprowski, Plotkin, WiktorWistar InstituteVaccine, Virology
1980Pasteur Institute filed for US patent for fractionation method to purify HBsAg from plasma to produce hepatitis B vaccineTiollaisPasteur InstituteVaccine
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
Jul 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, MerckVaccine
1 Jun 1984Genetically engineered vaccine against hepatitis B reported to have positive trial resultsScolnick, McLean, West, McAleer , Miller, BuynakMerck, University California San FranciscoRecombinant DNA, Vaccine
Jul 1984Taiwan launched nationwide hepatitis B vaccination programme  Vaccine
8 Sep 1985John F Enders diedEndersChildren's Hospital BostonVirology, Vaccine
1986Low-cost plasma vaccine against hepatitis B approved in Indonesia  Vaccine
1986First genetically engineered vaccine against hepatitis B approvedScolnickMerckRecombinant DNA, Vaccine
Nov 1986Low-cost plasma hepatitis B vaccine gained approval in South KoreaPrince, VnekCheil SugarVaccine
Dec 1986Genetically engineered hepatitis B vaccine, Engerix-B, approved in Belgium SmithKline BiologicalsVaccine, Recombinant DNA
1989Merck sold hepatitis B vaccination manufacturing technology to Chinese government for $7millionVagelosMerckVaccine
Jan 1989Genetically engineered hepatitis B vaccine, Engerix-B, approved in US SmithKline BiologicalsVaccine, Recombinant DNA
May 1989Genetically engineered hepatitis B vaccine, GenHevac, approved in France Pasteur VaccinsVaccine, Recombinant DNA
1990Hepatitis B vaccine cost US$3 per dose  Vaccine
1993Hepatitis B vaccination manufacturing plant opened in Beijing, aided by Merck MerckVaccine

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

US licensed first rabies vaccine for human use

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

1 Jun 1984

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

Jul 1984

Taiwan launched nationwide hepatitis B vaccination programme

8 Sep 1985

John F Enders died

1986

Low-cost plasma vaccine against hepatitis B approved in Indonesia

1986

First genetically engineered vaccine against hepatitis B approved

Nov 1986

Low-cost plasma hepatitis B vaccine gained approval in South Korea

Dec 1986

Genetically engineered hepatitis B vaccine, Engerix-B, approved in Belgium

1989

Merck sold hepatitis B vaccination manufacturing technology to Chinese government for $7million

Jan 1989

Genetically engineered hepatitis B vaccine, Engerix-B, approved in US

May 1989

Genetically engineered hepatitis B vaccine, GenHevac, approved in France

1990

Hepatitis B vaccine cost US$3 per dose

1993

Hepatitis B vaccination manufacturing plant opened in Beijing, aided by Merck