Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1995-12-28
1999-01-05
Woodward, Michael P.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
435 71, 435 691, 435 693, 435 701, 4351891, 4352401, 4353201, 4353251, 435975, 530350, 5303883, 5303894, 530806, 530810, 530826, 4241391, 4241891, 4241851, 4241931, 4242271, C07K 1402, C07K 1608, C12Q 170, G01N 3353
Patent
active
058560840
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to recombinant DNA molecules which code for polypeptides having specificity towards a hepatitis B viral antigen.
More particularly this invention relates to a vaccine composition for stimulating the production of antibodies in humans to a variant hepatitis B virus.
BACKGROUND OF THE INVENTION
The cloning of the genomes of hepatitis B virions of different serotypes is well known in the art (Miller et al). Dane particles which are hepatitis B virions and are isolatable from infected patients have a diameter of approximately 42 nm. Each consists of an envelope comprising the hepatitis B surface antigen (HBsAg), a capsid (HBcAg), an endogenous polymerase and a DNA genome. A third polypeptide, `e` antigen (HBeAg) is made by the hepatitis B virus and found in solubilized form in serum.
Infection with hepatitis B virus (HBV) is a serious, widespread problem but vaccines for use in mass immunisation are now widely available. Vaccines commercially available against HBV comprise hepatitis B virus surface antigen (HBsAg) either in native or recombinant form. The authentic (or wild type) hepatitis B virus surface antigen can be recovered from plasma of infected individuals as a particle of about 22 nm comprising of two proteins known as P24 and its glycosylated derivative GP28, both of which are encoded by a 226 amino acid coding sequence on the HBV genome known as the S protein coding sequence or HBV S-gene (Tiollais et al., (1985)). The complete amino acid sequence as well as the nucleotide sequence encoding, HBsAg is given in Valenzuela et al., Nature 280 815 (1979) (SEQ ID NO:1). The numbering system used by Tiollais et al. to define nucleotide and amino acid positions is used herein.
Insertion of HBV S-gene coding sequences under the control of yeast promoters on expression vectors to enable expression of HBsAg in S. cerevisiae for vaccine production has been described by Harford et al. in Develop. Biol. Standard 54 125 (1983), Valenzuela et al., Nature 298 347 (1982) and Bitter et al., J. Med. Virol. 25 123 (1988). Expression in Pichia pastoris has been described by Gregg et al., Biotechnology 5 479 (1987), (see also European Patent Publication No. 0226846) as has expression in Hansenula polymorpha (European Publication No. 0299108).
Vaccines have also been prepared from hybrid immunogenic particles comprising HBsAg protein as described in European Patent Publication No. 0278940. Such immunogenic particles can contain, for example, all or parts of the HBsAg precursor protein encoded by the coding sequence which immediately precedes the HBV-S gene on the HBV genome, referred to herein as the Pre-S coding sequence. The Pre-S coding sequence normally codes for 163 amino acids (in the case of the ay HBV sub type) and comprises a Pre-S1 coding sequence and a Pre-S2 coding sequence. The latter codes for 55 amino acids and immediately precedes the S protein coding sequence (European Publication No. EP-A-0278940).
The surface antigen (the S antigen) open reading frame of HBV-DNA is divided into three regions, pre-S1, pre S-2 and S. It encodes three envelope proteins of HBV termed: large, middle and major proteins. The major protein, HBsAg, consists of 226 amino acids and is encoded by the S gene (Tiollais et al., (1981); Tiollais et al., (1987) and Lau et al.). All three envelope proteins contain HBsAg antigenic sites and are easily detected by conventional immunoassays for HBsAg. These immunoassays are extensively used for diagnosing HBV infection and screening blood donors world-wide. The HBsAg reactivity is dependent on the structural conformation of the hydrophilic region from amino acids 124-147 which is defined as the `a` determinant (Ashton-Rickardt et al. and Brown et al.). This is common to all HBV subtypes and antibody to it confers protection against reinfection with any of the subtypes.
HBV-DNA sequences hybridising under highly stringent conditions with an HBV probe have been shown in the liver, serum and blood mononuclear cells of subjects negative for seru
REFERENCES:
patent: 5593825 (1997-01-01), Carman
patent: 5595739 (1997-01-01), Carman
Karayiannis Peter
Thomas Howard Christopher
Imperial College of Science Technology & Medicine
Woodward Michael P.
Zeman Mary K.
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