Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof
Patent
1996-02-12
1998-07-07
Knode, Marian C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Virus or component thereof
4241921, 4242021, 4242821, A61K 3929, A61K 3939
Patent
active
057764689
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP94/00818 filed Mar. 14, 1994.
The present invention relates to novel vaccine formulations, methods for preparing them and to their use in therapy.
3-O-deacylated monophosphoryl lipid A (or 3 De-O-acylated monophosphoryl lipid A) has formerly been termed 3D-MPL or d3-MPL to indicate that position 3 of the reducing end glucosamine is de-O-acylated. For preparation, see GB 2 220 211 A. Chemically it is a mixture of 3-deacylated monophosphoryl lipid A with 4, 5 or 6 acylated chains. Herein the term 3D-MPL (or d3-MPL) is abbreviated to MPL since `MPL` is a Registered Trademark of Ribi Immunochem., Montana which is used by Ribi to denote unambiguously their 3-O-deacylated monophosphoryl lipid A product.
GB 2 220 211A mentions that the endotoxicity of the previously used enterobacterial lipopolysacharides (LPS) is reduced while the immunogenic properties are conserved. However GB 2 220 211 cited these findings merely in connection with bacterial (Gram negative) systems. No mention of the particle size of the MPL was made. In fact the particle size of the known 3-O-deacylated monophosphoryl lipid A has particles in excess of 500 nm.
In WO 92/16231 a vaccine formulation comprising a Herpes Simplex Virus glycoprotein gD or immunological fragments thereof in conjunction with 3 deacylated monophosphoryl lipid A was disclosed. Again, no mention of the particle size of the 3 deacylated monophosphoryl lipid A was made.
In WO 92/06113 a vaccine formulation comprising HIV gp 160 or a derivative thereof such as gp 120 in conjunction with 3 deacylated monophosphoryl lipid A was disclosed. No mention of particle size of the MPL was made.
The present invention provides a vaccine composition comprising an antigen in conjunction with 3-O-deacylated monophosphoryl lipid A (abbreviated herein to MPL) and a suitable carrier wherein the particle size of the MPL is `small` and in general does not exceed 120 nm when prepared.
Such a formulation is suitable for a broad range of monovalent or polyvalent vaccines.
Surprisingly, it has been found that vaccine compositions according to the invention have particularly advantageous properties as described herein. In particular such formulations are highly immunogenic. Additionally sterility of the adjuvant formulation can be assured as the product is susceptible to sterile filtration. A further advantage of `small` MPL arises when formulated with aluminium hydroxide, as the MPL interacts with the aluminium hydroxide and the antigen to form a single entity.
In an embodiment of the invention, the antigen is a viral antigen, for example an antigen against hepatitis infection (Hepatitis A, B, C, D, or E) or herpes (HSV-1 or HSV-2) infection as described hereinbelow. A review on modern hepatitis vaccines, including a number of key references, may be found in the Lancet, May 12th 1990 at page 1142 ff (Prof A. L. W. F. Eddleston). See also `Viral Hepatitis and Liver Disease` (Vyas, B. N., Dienstag, J. L., and Hoofnagle, J. H., eds, Grune and Stratton, Inc. (1984) and `Viral Hepatitis and Liver Disease` (Proceedings of the 1990 International Symposium, eds F. B. Hollinger, S. M. Lemon and H. Margolis, published by Williams and Wilkins). References to HSV-1 and HSV-2 may be found in WO 92/16231.
Infection with hepatitis A virus (HAV) is a widespread problem but vaccines which can be used for mass immunisation are available, for example the product `Havrix` (SmithKline Beecham Biologicals) which is a killed `Inactivated Candidate Vaccines for Hepatitis A` by F. E. Andre, A Hepburn and E. D. Hondt, Prog Med. Virol. Vol 37, pages 72-95 (1990) and the product monograph `Havrix` published by SmithKline Beecham Biologicals (1991)!.
Flehmig et al (loc cit., pages 56-71) have reviewed the clinical aspects, virology, immunology and epidemiology of Hepatitis A and discussed approaches to the development of vaccines against this common viral infection.
As used herein the expression `HAV antigen` refers to any antigen capable of stimulating neutralising antibody to HAV in human
REFERENCES:
patent: 4196192 (1980-04-01), Kuo
patent: 4806352 (1989-02-01), Cantrell
patent: 4857634 (1989-08-01), Minor et al.
patent: 4877611 (1989-10-01), Cantrell
patent: 4912094 (1990-03-01), Myers et al.
patent: 5026557 (1991-06-01), Estis et al.
patent: 5100662 (1992-03-01), Bolcsak et al.
Azuma, "Synthetic Immunoadjuvants: application to non-specific host stimulation and potentiation of vaccine immunogenicity", Vaccine 10, 1000-1006 (1992).
Andre et al., "Inactivated Candidate Vaccines for Hepatitis A", Prog. Med. Virol. 37, 72-95 (1990).
Szoka et al., "Comparative Properties and Methods of Preparation of Lipid Vesicles (Liposomes)", Ann. Rev. Biophys. Bioeng. 9, 467-508 (1980).
Coursaget et al., "Simultaneous Administration of Diphtheria-Tetanus-Pertussis-Polio and Hepatitis B Vaccines in a Simplified Immunization Program", Infection and Immunity, 51(3), pp. 784-787 (1986).
Desmons Pierre
Garcon-Johnson Nathalie Marie-Josephe Claude
Hauser Pierre
Slaoui Moncef
Voet Pierre
Knode Marian C.
SmithKline Beecham Biologicals (S.A.)
Wortman Donna C.
LandOfFree
Vaccine compositions containing 3-0 deacylated monophosphoryl li does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Vaccine compositions containing 3-0 deacylated monophosphoryl li, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Vaccine compositions containing 3-0 deacylated monophosphoryl li will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1202624