Drug – bio-affecting and body treating compositions – Lymphokine – Interleukin
Reexamination Certificate
1998-03-05
2001-10-16
Mertz, Prema (Department: 1646)
Drug, bio-affecting and body treating compositions
Lymphokine
Interleukin
C424S184100, C424S190100, C424S198100, C514S002600, C514S008100, C514S012200, C514S054000, C514S885000
Reexamination Certificate
active
06303114
ABSTRACT:
BACKGROUND OF THE INVENTION
Non-protein antigens such as polysaccharides and lipids induce antibody responses without the need for T cells and are therefore referred to as T-independent (TI) antigens. However, because of the lack of involvement of T cell help, most TI antigens are relatively poor immunogens. In general, responses to TI antigens consist of IgM antibodies of low affinity, and do not show significant heavy chain class switching, affinity maturation, or memory. The practical significance of TI antigens is that many bacterial capsular and cell wall polysaccharides belong to this category and are therefore relatively poor at eliciting humoral immunity.
Young children and the elderly are particularly susceptible to life-threatening infections with encapsulated bacteria such as pneumococcus and meningococcus. It has been estimated by the Centers for Disease Control that in the U.S. per year,
Streptococcus pneumoniae
causes 3,000 cases of meningitidis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and 7 million cases of otitis media (middle ear infection). The World Health Organization has estimated that worldwide, this organism causes 100 million cases per year with 10 million deaths per year. Similarly,
Neisseria meningiditis
is the leading cause of meningitis in children and young adults with 2,600 cases/year in the U.S., 310,000 cases and 35,000 deaths per year worldwide.
Polysaccharide vaccines for inducing immunity to pathogens such as
S. pneumoniae
and
N. meningiditis
are available, but they are generally ineffective in children less than 2 years of age and are of limited efficacy in older individuals. In addition, in all recipients the vaccines, even in conjugate form, induce limited isotype switching. Clearly, alternative approaches for vaccination against pathogens having TI antigens are needed.
SUMMARY OF THE INVENTION
Applicants have found that interleukin-12 (IL-12) serves as a very strong adjuvant for eliciting immune responses (e.g., antibody (IgG) response) during T-cell independent (TI) immune responses, including responses to vaccine preparations which are currently used in humans. Thus, the present invention relates to a method of enhancing an immune response against a TI antigen (one or more) in a host. In one embodiment, the present invention relates to a method of inducing an immune response against a TI antigen in a host, which comprises administering to the host an effective amount of IL-12 and the TI antigen. In another embodiment, the present invention is a method of enhancing an immune response against a TI antigen in a host, which comprises administering to the host an effective amount of IL-12 and the TI antigen. The methods of the present invention can be used to induce and/or enhance an immune response to a TI antigen in a mammalian host, such as a primate (e.g., human), murine, feline, canine, bovine or porcine host. The invention also relates to compositions comprising IL-12 and a TI antigen.
The methods of the present invention can be used, for example, to induce and/or enhance a humoral immune response (e.g., IgG2a and/or IgG3 humoral immune response) in the host. The TI antigen can include, for example, a carbohydrate (e.g., a polysaccharide), a lipid, (e.g., liposomes, phosphorylcholine) a glycoprotein, a hapten-carrier conjugate, a lipopolysaccharide, or a phage (e.g., T4). The IL-12 and/or the TI antigen can be administered as a protein or as a polynucleotide under conditions in which the TI antigen and/or IL-12 is expressed in vivo.
In a particular embodiment, the present invention relates to a method of inducing and/or enhancing an immune response to
Streptococcus pneumoniae
in a host, which comprises administering to the host an effective amount of IL-12 and the TI antigen of
Streptococcus pneumoniae.
In another embodiment, the invention relates to a method of inducing and/or enhancing an immune response to
Neisseria meningiditis
in a host, which comprises administering to the host an effective amount of IL-12 and the TI antigen of
Neisseria meningiditis.
The invention also encompasses a composition comprising IL-12 and a TI antigen. One or more TI antigens can be used in the methods and compositions of the present invention.
Use of IL-12 as described herein provides effective methods and compositions which can be used to induce and/or enhance an immune response against a TI antigen.
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Buchanan Renee M.
Metzger Dennis W.
Hamilton Brook Smith & Reynolds P.C.
Mertz Prema
The Medical College of Ohio
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