Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1998-12-28
2004-02-10
Wehbe', Anne M. (Department: 1632)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S002600, C435S370000, C435S325000, C435S455000, C530S300000, C530S350000, C424S093200, C424S093210
Reexamination Certificate
active
06689757
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to vaccines and methods of vaccination which involve transfection of cells.
BACKGROUND OF THE INVENTION
Vaccination has been an important medical pursuit ever since it was observed that, for certain diseases, initial exposure to the infectious agent conferred lifelong immunity against subsequent infections. Vaccines have been used for many years in order to build immunity in an individual against infection by particular pathogenic organisms such as viruses, bacteria, fungi and parasites.
Early vaccines relied on live organisms or killed organisms that retained their immunogenicity. A better understanding of the structure and function of particular pathogens and of the mechanisms of adaptive immunity has made it possible to design safer and more directed vaccines. The current vaccine against Hepatitis B virus, for example, relies on inoculation using only a portion of the viral surface antigen, rather than the complete organism. Such directed vaccines lead to fewer side-effects and avoid unwanted immune responses to antigens that are not protective, i.e., do not confer lasting immunity.
Advanced vaccine design has made use of recombinant DNA technology and gene therapy concepts to provide DNA vaccines, wherein a vector for expression of a desired immunogen in mammalian cells is injected into a subject. The vector is taken up into cells around the site of injection, and then operates to express the immunogen in situ, which in turn leads to a protective immune response.
A problem associated with the use of DNA vaccines thus far is that the tissue into which the vector is typically injected, i.e., muscle, is not usually associated with antigen presentation. Consequently, the DNA vaccine does not produce a highly effective immune response.
There is a need for methods and specialized gene delivery vehicles suitable for delivery of complex antigens to cells so that the resulting antigen presentation is capable of activating substantially all of the components of the adaptive immune system, i.e., capable of eliciting the immune response necessary to combat a particular pathogen whether mediated by antibodies, cytotoxic T cells, helper T cells, natural killer cells, or macrophages.
SUMMARY OF THE INVENTION
The present invention provides methods and compositions for obtaining long-lasting immunity via delivery to an antigen presenting cell a complex comprising a nucleic acid encoding a first epitope, and a peptide containing a second epitope.
Antigen presenting cells present antigenic epitopes of antigens to T cells in association with either Class I or Class II MHC molecules. Endogenously synthesized proteins are generally presented in association with Class I whereas proteins taken up from the environment (exogenously synthesized proteins) are generally presented in association with Class II. It is therefore beneficial for a vaccine to produce presentation of the required antigen to both Class I and II MHC molecules. The invention provides for stimulation of both class I and II presentation by providing antigen to an antigen presenting cell in the form of an endogenously synthesized protein (i.e., a nucleic acid-encoded epitope) and an exogenously synthesized protein.
It is believed that the dual delivery to an antigen presenting cell of an epitope, or antigen, in its peptide or polypeptide form, together with a second nucleic acid encoded epitope results in an enhanced immune response.
The invention therefore encompasses a method of vaccinating a mammal against a disease, comprising administering to said mammal a mixture of (i) a nucleic acid encoding a first epitope and (ii) a peptide comprising a second epitope such that the nucleic acid and the peptide are taken up by and the nucleic acid is expressed in a professional antigen presenting cell of the mammal, wherein an immune response is elicited in the mammal to the epitopes.
The invention also encompasses a method of vaccinating a mammal against a disease wherein the mixture administered comprises a complex comprising (i) a nucleic acid encoding a first epitope and (ii) a peptide comprising a second epitope such that the complex is taken up by and expressed in a professional antigen presenting cell of the mammal, wherein an immune response is elicited in the mammal to the first and second epitopes.
The invention also encompasses a method of vaccinating a mammal against a disease, comprising administering, to the mammal professional antigen presenting cells containing (i) a recombinant nucleic acid encoding a first epitope and (ii) a second epitope that is not normally present in the antigen presenting cells and, wherein upon administration an immune response is elicited in the mammal to the epitopes.
The invention also encompasses a composition for vaccinating a mammal against a disease, comprising a complex comprising (i) a vector comprising a nucleic acid encoding a first epitope and a sequence which permits maintenance of the vector in episomal form , and (ii) a peptide containing a second epitope, wherein said composition is adapted for delivery to or selective expression in antigen presenting cells.
The invention also encompasses a complex for vaccinating a mammal against a disease, comprising professional antigen presenting cells containing (i) a recombinant nucleic acid encoding a first epitope and (ii) a peptide containing a second epitope that is not normally present in the antigen presenting cells.
The invention encompasses a method of vaccinating a mammal against a disease, comprising administering to the mammal a complex comprising (i) a nucleic acid and (ii) a peptide including an epitope such that the complex is taken up by a professional antigen presenting cell of the mammal, wherein an immune response is elicited in the mammal to the epitope.
In this aspect of the invention, it is believed that the presence of the nucleic acid in the mixture promotes uptake by antigen presenting cells of the peptide containing an epitope so as to promote an immune response to the epitope.
Preferably, the first epitope is from an infectious agent or an organism, and the first epitope is present in the mammal during the course of a disease.
It is preferred that the complex further comprises a second epitope, and that the first and second epitopes are epitopes of the same antigen, or epitopes of the same infectious agent or organism.
For example, the first and/or second epitope may comprise an immunodominant epitope of influenza NP.
It is also preferred that the complex or mixture further comprises a second peptide that contains an epitope that is different from the epitope contained in the peptide referred to in (ii) above.
The complex may further comprise a cell-targeting ligand for targeting professional antigen presenting cells.
It is preferred that the nucleic acid is intimately associated with the peptide containing the epitope such that the nucleic acid is preferably in condensed form.
Therefore, it also is preferred that the first epitope is present in a two-domain polypeptide comprising the first epitope fused to a nucleic acid-binding amino acid sequence. As used herein, the term “epitope” refers to an immunogenic amino acid sequence. An epitope may refer to a minimum amino acid sequence of 6-8 amino acids (i. e., a peptide), which minimum sequence is immunogenic when removed from its natural context and is carried in a complex according to the invention as a peptide, or when transplanted into a heterologous polypeptide such that it retains its natural immunogenicity and thus is carried in a complex according to the invention as part of a polypeptide. An epitope also may refer to that portion of a natural polypeptide which is immunogenic, where the natural polypeptide containing the epitope is referred to as an antigen. Of course, a polypeptide or antigen may contain one or more distinct epitopes. An epitope also may refer to an immunogenic portion of a multichain polypeptide, i.e., which is encoded by distinct open reading frames. The terms epitope, peptide, and polypep
M.L. Laboratories PLC
O'Connor P.C. Cozen
Wehbe' Anne M.
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