Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
  • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
  • C12N2740/00—Reverse transcribing RNA viruses
  • C12N2740/00011—Details
  • C12N2740/10011—Retroviridae
  • C12N2740/16011—Human Immunodeficiency Virus, HIV
  • C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
  • C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Definitions

• T-4 lymphocytes also known as helper or inducer cells, interact with other specialized cell types of the immune system to confer immunity to or defense against infection. More specifically, T-4 lymphocytes stimulate production of growth factors which are critical to the functioning of the immune system. For example, they activate macrophages ("killer cells”) to attack infected or otherwise abnormal host cells, and induce monocytes (“scavenger cells”) to encompass and destroy invading microbes. They also induce maturation of B lymphocytes into cells which produce defensive antibodies to specific antigens.
• killer cells macrophages
• scavenger cells monocytes
• This complex immune defense system may be partially or totally disrupted as a result of a given therapeutic regimen.
• chemotherapy and radiation therapies used to treat malignant diseases, or immunosuppressants administered to prevent rejection of transplanted organs often cause selective destruction of circulating T-4 lymphocytes or contribute to other T lymphocyte abnormalities in the patient undergoing treatment.
• Such side effects of these treatments may lead to complete immunosuppression and attendant susceptibility of the patient to a wide range of opportunistic infections. Even when immunosuppression is not complete, in those patients having depleted T lymphocyte populations, exposure to a given antigen alone may not be sufficient to elicit the formation of antibodies.
• T-4 lymphocytes Upon infection of a host, the primary targets of the HIV virus, T-4 lymphocytes, are rendered non-functional. In addition to T-4 lymphocytes, the HIV virus are also been shown to infect central nervous system cells, macrophages and B lymphocytes [J. M. Ismach, "AIDS: Can The National Cope", Medical World News (March 25, 1985)].
• the present invention solves the problems referred to above by providing immunotherapeutic methods and compositions for use in the treatment of immunodeficient patients.
• the methods and compositions of this invention are characterized by immunogens which comprise antigens specific for a target infection coupled to T-cell independent carriers.
• human immunodeficiency virus HIV
• HTLV-III human T-cell lymphotropic virus type III
• LAV lymphadenopathy-associated virus
• ARV AIDS-associated retrovirus
• Figure 1 depicts the amino acid sequences of each of peptides 1-2, 4-6, 31, 64 and 78 used in one embodiment of the antigen/T-cell independent carrier conjugates of this invention, as well as that of the region between amino acid 600 and amino acid 750 of the HIV env gene.
• the amino acids are represented by single letter codes as follows:
• Antigens which may be coupled to T-independent carriers to form immunogenic conjugates according to this invention include peptides involved in the pathogenesis of the HIV virus.
• Such peptides include peptides from the env region of the HIV genome, for example, peptides characterized by an amino acid sequence derived substantially from the region between about amino acid 600 and amino acid 750 of the HIV env gene or the D-retro forms of those peptides -- those produced by synthesis with D amino acids in the opposite orientation, beginning with the carboxy terminal amino acid of the L form.
• the antigen/ T-cell independent carrier conjugate is employed in the methods and compositions of this invention in a conventional manner.
• the coupled antigen alone or in combination with other coupled antigens of this invention, may be mixed with one or a combination of well-recognized adjuvants and additives, preferably by first dissolving the coupled antigen, for example, in PBS with 0.1% SDS.
• coupled antigens may be linked to hydrophobic groups to build the adjuvant into the composition.
• the coupled antigen may be administered to a patient in combination with lymphokines, such as B cell growth factors, which are known to stimulate the activity of B lymphocytes.
• compositions may be employed using the antigen/T-cell independent carrier conjugates of this invention.
• the above-prepared compositions are then employed in a conventional manner for the treatment of opportunistic infections in immunodeficient patients.
• Such methods of treatment and their dosage levels and requirements are well-recognized in the art and may be chosen by those of skill in the art from available methods and techniques.
• the conjugates of this invention may be combined with a pharmaceutically acceptable adjuvant for administration to patient in a pharmaceutically acceptable manner and in an amount effective to elicit antibodies specific for the target infection and to lessen the severity of that infection.
• the dosage and treatment regimens will depend upon factors such as the patient's health status, the severity and course of infection and the judgment of the treating physician.
• the antigen/T-cell independent carrier conjugates of this invention are useful in vaccines and methods for protecting immunodeficient humans against opportunistic infections for at least some period of time.
• the conjugates may be employed in these vaccines and methods either alone or together with other conjugates of this invention in a manner consistent with the conventional utilization of antigens in vaccines.
• the antigen/T-cell independent carrier conjugates of this invention may be combined with pharmaceutically acceptable adjuvants conventionally employed in vaccines and administered in immunologically effective amounts to protect immunodeficient patients for some time against opportunistic infections.
• the immunogenic conjugates may be combined with B lymphocyte-stimulating factors for administration as a vaccine.
• Example 2 Coupling Of An HIV-Peptide To A Carboxymethyl Ficoll Carrier
• carboxymethyl Ficoll according to the procedure described in J. K. Inman, "Thymus- Independent Antigens: The Preparation Of Covalent, Hapten-Ficoll Conjugates", J. Immunol., 114, pp. 704-09 (1975).
• PBS saline-PO 4
• PBS-Tween-20 0.05%
• each plate had a series of "background" control wells containing no test serum and to which one of the following had been added: -- saline-PO 4 (EBS) containing 20% normal goat serum -- PBS-Tween-20 (0.05%) containing 1% normal goat serum and goat - anti-mouse-IgM HRP at a dilution of 1:4000
• test plate also had a negative and positive control serum.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Biophysics (AREA)
• Biochemistry (AREA)
• Gastroenterology & Hepatology (AREA)
• General Health & Medical Sciences (AREA)
• Genetics & Genomics (AREA)
• Medicinal Chemistry (AREA)
• Molecular Biology (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Virology (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Peptides Or Proteins (AREA)

Applications Claiming Priority (2)

Publications (2)

Family

ID=21920469

Family Applications (1)

Country Status (3)

Families Citing this family (22)

Family Cites Families (4)

• 1988
  • 1988-04-19 AU AU17118/88A patent/AU1711888A/en not_active Abandoned
  • 1988-04-20 EP EP19880904102 patent/EP0311675A4/de not_active Withdrawn
  • 1988-04-20 WO PCT/US1988/001213 patent/WO1988008429A1/en not_active Ceased

Also Published As

Similar Documents

Legal Events