Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1995-10-10
1999-01-26
Smith, Lynette F.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 2372, 435 691, 435 693, 530350, 530395, C07H 2102, C07H 2104, C12P 2106, C07K 100
Patent
active
058640274
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to the rational design and preparation of HIV vaccines based on HIV envelope polypeptides and the resultant vaccines. This invention further relates to improved methods for HIV serotyping and immunogens which induce antibodies useful in the serotyping methods.
BACKGROUND OF THE INVENTION
Acquired immunodeficiency syndrome (AIDS) is caused by a retrovirus identified as the human immunodeficiency virus (HIV). There have been intense effort to develop a vaccine. These efforts have focused on inducing antibodies to the HIV envelope protein. Recent efforts have used subunit vaccines where an HIV protein, rather than attenuated or killed virus, is used as the immunogen in the vaccine for safety reasons. Subunit vaccines generally include gp120, the portion of the HIV envelope protein which is on the surface of the virus.
The HIV envelope protein has been extensively described, and the amino acid and RNA sequences encoding HIV envelope from a number of HIV strains are known (Myers, G. et al., 1992. Human Retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences. Los Alamos National Laboratory, Los Alamos, N. Mex.). The HIV envelope protein is a glycoprotein of about 160 kd (gp160) which is anchored in the membrane bilayer at its carboxyl terminal region. The N-terminal segment, gp120, protrudes into the aqueous environment surrounding the virion and the C-terminal segment, gp41, spans the membrane. Via a host-cell mediated process, gp160 is cleaved to form gp120 and the integral membrane protein gp41. As there is no covalent attachment between gp120 and gp41, free gp120 is released from the surface of virions and infected cells.
The gp120 molecule consists of a polypeptide core of 60,000 daltons which is extensively modified by N-linked glycosylation to increase the apparent molecular weight of the molecule to 120,000 daltons. The amino acid sequence of gp120 contains five relatively conserved domains interspersed with five hypervariable domains. The positions of the 18 cysteine residues in the gp120 primary sequence, and the positions of 13 of the approximately 24 N-linked glycosylation sites in the gp120 sequence are common to all gp120 sequences. The hypervariable domains contain extensive amino acid substitutions, insertions and deletions. Sequence variations in these domains result in up to 30% overall sequence variability between gp120 molecules from the various viral isolates. Despite this variation, all gp120 sequences preserve the virus's ability to bind to the viral receptor CD4 and to interact with gp41 to induce fusion of the viral and host cell membranes.
gp120 has been the object of intensive investigation as a vaccine candidate for subunit vaccines, as the viral protein which is most likely to be accessible to immune attack. gp120 is considered to be a good candidate for a subunit vaccine, because (i) gp120 is known to possess the CD4 binding domain by which HIV attaches to its target cells, (ii) HIV infectivity can be neutralized in vitro by antibodies to gp120, (iii) the majority of the in vitro neutralizing activity present in the serum of HIV infected individuals can be removed with a gp120 affinity column, and (iv) the gp120/gp41 complex appears to be essential for the transmission of HIV by cell-to-cell fusion.
The identification of epitopes recognized by virus neutralizing antibodies is critical for the rational design of vaccines effective against HIV-1 infection. One way in which antibodies would be expected to neutralize HIV-1 infection is by blocking the binding of the HIV-1 envelope glycoprotein, gp120, to its cellular receptor, CD4. However, it has been surprising that the CD4 blocking activity, readily demonstrated in sera from HIV-1 infected individuals (31, 44) and animals immunized with recombinant envelope glycoproteins (1-3), has not always correlated with neutralizing activity (2, 31, 44). Results obtained with monoclonal antibodies have shown that while some of the monoclonal antibodies that bloc
REFERENCES:
patent: 4725669 (1988-02-01), Essex et al.
patent: 5166050 (1992-11-01), Shriver et al.
patent: 5420030 (1995-05-01), Reitz, Jr. et al.
patent: 5576000 (1996-11-01), Reitz, Jr. et al.
Allan et al., "Major Glycoprotein Antigens that Induce Antibodies in AIDS Patients are Encoded by HTLV-III,"Science 228:1091-1094 (May 31, 1985).
Anderson et al., "Effect of Dose and Immunization Schedule on Immune Response of Baboons to Recombinant Glycoprotein 120 of HIV-1," The Journal of Infectious Diseases 160(6):960-969 (Dec. 1989).
Arthur et al., "Challenge of Chimpanzees (Pan troglodytes) Immunized with Human Immunodeficiency Virus Envelope Glycoprotein gp120," Journal of Virology 63(12):5046-5053 (Dec. 1989).
Barin et al., "Virus Envelope Protein of HTLV-III Represents Major Target Antigen For Antibodies in AIDS Patients," Science 228:1094-1096 (May 31, 1985).
Barrett et al., "Large-scale Production and Purification of a Vaccinia Recombinant-Derived HIV-1 gp160 and Analysis of Its Immunogenicity," AIDS Research And Human Retroviruses 5(2):159-171 (1989).
Berman et al., "Protection from Genital Herpes Simplex Virus Type 2 Infection by Vaccination with Cloned Type 1 Glycoprotein D," Science 227:1490-1492 (Mar. 1985).
Berman et al., "Human Immunodeficiency Virus Type.1 Challenge of Chimpanzees Immunized with Recombinant Envelope Glycoprotein gp120," Proc. Natl. Acad. Sci. USA 85:5200-5204 (Jul. 1988).
Berman et al., "Expression and Immunogenicity of the Extracellular Domain of the Human Immunodeficiency Virus Type-1 Envelope Glycoprotein, gp160," Journal of Virology 63(8):3489-3498 (Aug. 1989).
Chakrabarti et al., "Expression of the HTLV-III Envelope Gene by a Recombiant Vaccinia Virus," Nature320:535-537 (Apr. 10, 1986).
Clements et al., "The V3 Loops of the HIV-1 and HIV-2 Surface Glycoproteins Contain Proteolytic Cleavage Sites: A Possible Function in Viral Fusion?" Aids Research And Human Retroviruses 7(1):3-16 (1991).
Clements, Certificate of Analysis, Celltech Limited, 2 pages (Jan. 23, 1990).
Desrosiers et al., "Vaccine Protection Against Simian Immunodeficiency Virus Infection," Proc. Natl. Acad. Sci. USA 86:6353-6357 (Aug. 1989).
NIH Conference, "Development and Evaluation of a Vaccine for Human Immunodeficiency Virus (HIV) Infection," Annals of Internal Medicine 110(5):373-385 (Anthony S. Fauci, moderator, Mar. 1, 1989).
Homsy et al., "The Fc and Not CD4 Receptor Mediates Antibody Enhancement of HIV Infection in Human Cells," Science 244:1357-1360 (Jun. 16, 1989).
Hu et al., "Expression of AIDS Virus Envelope Gene in Recombinant Vaccinia Viruses," Nature 320:537-540 (Apr. 10, 1986).
Hu et al., "Effect of Immunization with a Vaccinia-HIV env Recombinant on HIV Infection of Chimpanzees,"Nature 328:721-723 (Aug. 20, 1987).
Kitchen et al., "Aetiology of AIDS--Antibodies to Human T-cell Leukaemia Virus (Type III) in Haemophiliacs," Nature 312:367-369 (Nov. 22, 1984).
Krust et al., "Characterization of a Monoclonal Antibody Specific for the HIV-1 Precursor Glycoprotein," AIDS2(1):17-24 (1988).
Lasky et al., "Neutralization of the AIDS Retrovirus by Antibodies to a Recombinant Envelope Glycoprotein,"Science 233:209-212 (Jul. 11, 1986).
Lasky et al., "Delineation of a Region of the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein Critical for Interaction with the CD4 Receptor," Cell 50:975-985 (Sep. 11, 1987).
Lasky, "Current Status of the Development of an AIDS Vaccine," Critical Reviews in Immunology 9(3):153-172 (1989).
Letvin et al., "AIDS-like Disease in Macaque Monkeys Induced by Simian Immunodeficiency Virus: A Vaccine Trial," Vaccines, pp. 209-213 (1987).
Looney et al., "Type-restricted Neutralization of Molecular Clones of Human Immunodeficiency Virus," Science241:357-359 (Jul. 15, 1988).
Matsushita et al., "Characterization of a Human Immunodeficiency Virus Neutralizing Monoclonal Antibody and Mapping of the Neutralizing Epitope," Journal of Virology 62(6):2107-2114 (Jun. 1988).
Modrow et al., "Computer-assisted Analysis of Envelope Protein
Berman Phillip W.
Nakamura Gerald R.
Genentech Inc.
Haliday Emily M.
Smith Lynette F.
Terlizzi Laura
LandOfFree
HIV envelope polypeptides does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with HIV envelope polypeptides, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and HIV envelope polypeptides will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1451404