Autoimmune inflammatory diseases occur in greater than five percent of the United States population; this disease group includes asthma, multiple sclerosis, rheumatoid arthritis, and lupus. Treatments generally include immunosuppressants or anti-inflammatory drugs, which can have serious side effects; recently, more specific immunomodulatory therapies such as TNF-alpha antagonists have been developed.

Gene therapy and gene transfer have recently been recognized as effective therapeutic tools to combat diseases. Accordingly, market demands for vectors and carriers to facilitate such interventions have surged in recent years. Retroviral vectors provide an efficient and safe means of gene transfer to eukaryotic cells. The present invention relates to genetic engineering involving retrovirus packaging cells that produce retroviral vectors.

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of autoimmune diseases and T cell malignancies. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of malignant T cells and resting T cells. The transient ablation of resting T cells can "reset" the immune system by accentuating tolerizing responses. The toxin portion of the immunotoxin is genetically engineered to maintain bioactivity when recombinantly produced in Pichia pastoris.

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of rejection response in a patient, including graft-versus-host disease and transplantation of organs, tissues and cells into a host. In a specific embodiment of the invention, the transplant involves pancreatic islet cells. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of resting T cells, resulting in an accentuation of immune tolerizing responses and an increased tolerance to transplants and grafts.

The invention concerns immunotoxins and methods of making the immunotoxins. Targeting of the immunotoxins occurs via an antibody that is specific to T cells. This allows the specific ablation of malignant T cells and resting T cells. The transient ablation of resting T cells can "reset" the immune system by accentuating tolerizing responses. As a result, the immunotoxin can be used to treat autoimmune disease, malignant T cell-related cancers, and graft-versus-host disease.

The present research tool is a knockout mouse model (FPR^-/-) that lacks the high affinity N-formylpeptide receptor (FPR), created by targeted gene disruption.

Anthrax, whether resulting from natural or bioterrorist-associated exposure, is a constant threat to human health. The lethality of anthrax is primarily the result of the effects of anthrax toxin, which has 3 components: a receptor-binding protein known as "protective antigen" (PA) and 2 catalytic proteins known as "lethal factor" (LF) and "edema factor" (EF). Although production of an efficient anthrax vaccine is an ultimate goal, the benefits of vaccination can be expected only if a large proportion of the population at risk is immunized.

The disease burden associated with dengue virus infection has increased over the past several decades in the tropical and semi-tropical regions of the world, where over 2 billion people live at risk of dengue infection. Annually, there are an estimated fifty (50) to one hundred (100) million cases of dengue fever, making development of an effective vaccine a priority. In addition, there is a need for a "travelers vaccine" to protect those visiting dengue virus endemic areas, similar in scope to other currently available "travelers vaccines", such as hepatitis A vaccine.

Since the onset of the AIDS epidemic more than two decades ago, enormous efforts have been directed to making a vaccine that will protect against human immunodeficiency virus-1 (HIV); an effective vaccine is thought to require the induction of cellular and humoral responses. Vaccine candidates have included a variety of HIV immunogens delivered as DNA, attenuated poxviruses, adenoviruses, vesicular stomatitis virus, proteins, and various combinations thereof. The inventors' efforts to design an HIV vaccine have focused on modified vaccinia virus Ankara (MVA) as a vector.

Over the past decade, Staphylococcus epidermidis has become the most prevalent pathogen involved in nosocomial infections. Usually an innocuous commensal microorganism on human skin, this member of the coagulase-negative group of staphylococci can cause severe infection after penetration of the epidermal protective barriers of the human body. In the U.S. alone, S. epidermidis infections on in-dwelling medical devices, which represent the main type of infection with S. epidermidis, cost the public health system approximately $1 billion per year. Importantly, S.