Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Recombinant virus encoding one or more heterologous proteins...
Patent
1996-07-29
1998-04-14
Railey, II, Johnny F.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Recombinant virus encoding one or more heterologous proteins...
424 932, 4242781, 4353201, 514 44, A61K 3900, A61K 4505, A61K 4800, C12N 1586
Patent
active
057388520
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to methods of preventing new infections, curing current infections and treating chronic infections caused by intracellular infectious agents. The methods encompass using gene therapy to enhance the interaction between ligands that costimulate T cell activation. More specifically, this invention relates to materials and methods of gene therapy in which genes encoding an antigen from an infectious agent and ligands that costimulate T cell activation are co-expressed in the cells of the host animal to prevent or treat chronic infection. This method stimulates or enhances immune responses To antigens of infectious agents by enhancing the antigen-specific T cell response thus providing protection against new infection or terminating chronic infection.
BACKGROUND OF THE INVENTION
Many infectious agents are capable of causing infection and disease in a host organism; examples of such infectious agents include protozoa, fungi, bacteria, viruses and even worms. Of these infectious agents, those with the mechanism to act intracellularly pose the most significant challenge for prevention and treatment. This is particularly true where the host of the intracellular infectious agent is a mammal, such as man.
Mammals have a complex immune system which has several different mechanisms for defending against an invasion by an infectious agent. Under normal circumstances, the immune system functions to ultimately eliminate the infectious agent from the mammalian host's system. Most infections are self-limiting because the mammalian immune system is generally able to eliminate the infectious agents. Problems arise, however, when the immune system is unable to, or does not, respond to the presence of an infectious agent. In this scenario, infections can become chronic and can persist for many years or even the life-time of the infected human or animal, often resulting in serious disease.
Traditional, standard vaccines expose the immune system to a foreign antigen such as those of infectious agents to elicit an antigen-specific immune response. The immune response is most often humoral and not cellular, that is, it results in production of antibodies but not T cell-based immunity as discussed below. Effective vaccination prevents infection or modifies diseases resulting from infection caused by the infectious agent to which the vaccine is directed.
Immune responses that elicit neutralizing antibodies are sufficient for preventing infections with certain viruses. Murphy et al. (1990). Thus, infection by these viruses can be prevented by vaccination with antigens that elicit neutralizing antibodies. For some viruses and non-virus infectious agents, however, neutralizing antibodies either cannot be elicited or, if elicited, are insufficient to prevent infection and/or disease progression.
Two traditional vaccine types are killed viruses and live attenuated viruses. Killed viruses consist of either whole virions or other infectious agents the infectivity of which has been inactivated. These vaccines may also consist of antigenic subunits or component parts of virions or other infectious agents. These vaccines are administered by parenteral inoculation or exposure to mucous membranes. Live attenuated vaccines consist of live virus or other infectious agents with genetically altered virulence. When used for vaccination, these vaccines cause a reduced form of the disease, or no disease at all.
A third vaccine approach has been investigated and used experimentally but is not yet in clinical use. This approach is the utilization of live agents such as viruses or bacteria as vectors to express vaccine antigens of heterologous infectious agents. A gene or nucleotide sequence encoding the antigen is expressed by the vector and when used in vaccination, exposes the host to the antigen. An immune response to the antigen is expected to protect the host from the infectious agent from which the antigen was derived.
Examples of killed vaccines include tetanus toxoid, influenza virus subunit, rabi
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Chu Keting
Robinson William S.
Railey II Johnny F.
Solis Therapeutics, Inc.
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