Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
2001-02-13
2003-09-30
Saunders, David (Department: 1644)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C424S009200, C435S006120
Reexamination Certificate
active
06627407
ABSTRACT:
BACKGROUND OF THE INVENTION
Among the greatest successes in the field of public health is widespread vaccination against a variety of formerly common infectious diseases. For example, public vaccination programs in the United States have eradicated smallpox and dramatically reduced the incidence of diseases such as measles, rubella, polio and diphtheria, among others. However, the development of novel vaccine compositions is still an active area of research. In particular, the development of effective vaccines for a number of diseases for which no clinically proven vaccine exists remains an important goal. For example, a vaccine which protects against infection by human immunodeficiency virus (HIV) is a primary goal in efforts to control the spread of AIDS. Also needed are vaccine compositions which have improved efficacy in comparison to vaccines in current use.
The efficacy of a vaccine for use in humans depends upon the ability of the vaccine formulation to elicit an immune response which is sufficient to provide protection against subsequent challenge with the pathogen. Experimental vaccines are typically evaluated first in vivo in small animals, such as mice, guinea pigs or rabbits. The assessment of the experimental vaccines generally relies upon measurements of serum antibody responses and, sometimes, antigen-specific lymphocyte proliferative responses. Vaccine formulations which are successful in these animal models are then tested in sub-human primates and, finally, in humans.
The assessment of a test vaccine in an animal model is costly and takes considerable time. Typically, several doses of vaccine are administered to the animal at intervals of several weeks. The immune response of primates to a given test vaccine is often less than that of smaller animals, and clinical studies in humans are ultimately required to determine the efficacy of a test vaccine. In addition to the large costs associated with purchasing and housing animals for long periods of time, each step of the process requires a minimum of several months. Thus, the number of experimental vaccines which can be evaluated using prior art methods is necessarily limited, with the possible result that potentially useful vaccine formulations may never be tested.
There is, therefore, a need for an in vitro test for determining the human immune response to an experimental vaccine construct which would allow the rapid evaluation of large numbers of candidate vaccine compositions within a short time period and at reasonable cost.
SUMMARY OF THE INVENTION
The present invention relates to a method for assessing the ability of a candidate vaccine composition to stimulate a T cell response. In one embodiment, the invention provides a method for selecting one or more vaccine compositions from among a group of vaccine compositions for in vivo assessment, for example, in one or more animal or human subjects. Each of the vaccine compositions comprises one or more antigens or one or more nucleic acid molecules encoding one or more antigens. The method comprises the steps of: (1) contacting antigen presenting cells in culture with a vaccine composition selected from among the group of vaccine compositions, thereby, if one or more of the antigens or nucleic acid molecules can be taken up and processed by the antigen presenting cells, producing one or more processed antigens; (2) contacting the antigen presenting cells with T cells under conditions sufficient for the T cells to respond to one or more of the processed antigens; (3) determining whether the T cells respond to one or more of the processed antigens; whereby if the T cells respond to one or more of the processed antigens, then the vaccine composition stimulates a T cell response; and (4) repeating steps (1), (2) and (3) with each additional vaccine composition in the group, thereby identifying the vaccine compositions within the group which stimulate a T cell response; and, if one or more of these vaccine compositions stimulates a T cell response, (5) selecting at least one vaccine composition which stimulates a T cell response for assessment in one or more animals and/or in one or more human subjects.
In another embodiment, the invention relates to a method of selecting a vaccine composition from a group consisting of two or more vaccine compositions for assessment in one or more animals or in one or more human subjects. Each of the vaccine compositions comprises one or more antigens or one or more nucleic acid molecules encoding one or more antigens. The method comprises the steps of: (1) contacting antigen presenting cells in culture with a vaccine composition selected from among said group of vaccine compositions, thereby, if one or more of the antigens or nucleic acid molecules are taken up and processed by the antigen presenting cells, producing one or more processed antigens; (2) contacting the antigen presenting cells with T cells under conditions sufficient to produce a T cell response to one or more of the processed antigens, thereby producing a vaccine composition-stimulated T cell response; (3) measuring the vaccine composition-stimulated T cell response; (4) repeating steps (1), (2) and (3) with each of the remaining vaccine compositions in the group, thereby identifying the vaccine composition or compositions which stimulate the greatest T cell response; (5) selecting the vaccine composition or compositions which stimulate the greatest T cell response for assessment in one or more animals and/or in one or more human subjects.
In a further embodiment, the invention relates to a method for assessing the ability of a vaccine composition comprising one or more antigens or one or more nucleic acid molecules encoding one or more antigens to stimulate a protective T cell response. The method comprises the steps of: (1) contacting human antigen presenting cells in culture with the vaccine composition, thereby, if one or more of the antigens or nucleic acid molecules can be taken up and processed by the antigen presenting cells, producing one or more processed antigens; (2) contacting the antigen presenting cells with human T cells under conditions sufficient to produce a T cell response to one or more of the processed antigens, thereby producing a T cell response; (3) measuring the T cell response; and, if the T cell response is greater than a pre-selected value, (4) assessing the ability of the vaccine composition to stimulate a protective T cell response in one or more animals or in one or more human subjects.
In another embodiment, the method of the invention comprises the steps of: (1) contacting human antigen presenting cells in culture with the vaccine composition, whereby, if one or more of the antigens are taken up and processed by the antigen presenting cells, said antigen or antigens are processed by the antigen presenting cells, thereby producing one or more processed antigens; (2) contacting the antigen presenting cells of step (1) with human T cell clones which are specific for an epitope within one or more of the antigens for a period of time sufficient for the human T cell clones to respond to one or more of the processed antigens; and (3) determining whether the human T cell clones respond to the processed antigen or antigens. If the T cell clones respond to the processed antigen or antigens, the method can, optionally, further include the step of assessing the vaccine composition in one or more animals or human subjects.
Preferably, the vaccine composition includes at least one antigen which comprises a T cell epitope, and the T cells are T cell clones which are specific for a T cell epitope in at least one of the antigens. In one embodiment, the T cells are CD8
+
T cells and the vaccine composition includes at least one antigen comprising antigen a CD8 epitope. In this embodiment, the T cell response to the processed antigen can be, for example, T cell proliferation, cytolysis of the antigen presenting cells or the production of one or more cytokines.
In another embodiment, the T cells are CD4
+
T cells and the vaccine composi
Hamilton Brook Smith & Reynolds P.C.
Saunders David
University of Massachusetts Medical Center
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