Abzyme Research Foundation Announces Promising HIV Vaccine Candidate

/PRNewswire/ -- The Abzyme Research Foundation announces today that Dr. Sudhir Paul, a scientist at University of Texas Houston Medical School, has identified an important immunological deficiency in HIV-infected patients and has created a promising HIV vaccine candidate that rectifies the deficiency. The discoveries were presented on July 19th and 20th, 2010 at the XVII International AIDS Society Conference in Vienna, Austria.

The HIV vaccine candidate has been tested in mice and rabbits. It was effective in inducing the production of protective antibodies that stopped the HIV from infecting human blood cells in laboratory tests.

Dr. Paul and his colleagues discovered that HIV patients do not produce sufficient protective antibodies of a type called IgG that are capable of attacking the vulnerable CD4 binding site on the HIV. The virus binds to human host cells through this site to cause infection. The CD4 binding site is a small part of gp120, a protein found on the surface of HIV. Studies of mice injected with gp120 confirmed an insufficient IgG response to the CD4 binding site. Previous vaccine tests by other researchers used the gp120 protein itself without success in protecting against infection.

"Using an electron-seeking form of gp120, we triggered the production of the crucial IgG antibodies to the CD4 binding site in animals," said Dr. Paul. "We believe this method is the key to developing an HIV vaccine."

Dr. Paul's team has found that chemical stimulation of the immune system by electron-seeking (electrophilic) proteins is the central step for rectifying the defective antibody response to the CD4 binding site. Since the structure of the CD4 binding site is very similar in all HIV strains throughout the world, a globally effective HIV vaccine may be possible.

Lead E-VAC Candidate

The researchers have developed a synthetic electrophilic vaccine candidate, or E-VAC, which works by focusing the antibody response at the CD4 binding site. The E-VAC is a synthetic portion of gp120 that successfully mimics the shape of the CD4 binding site expressed by the HIV virus. Administration of E-VAC to animals induces antibodies with enzymatic activity, or abzymes. Unlike traditional antibodies that neutralize the target on a 1:1 basis, abzymes are significantly more efficacious because each abzyme molecule can neutralize thousands of target molecules.

E-VAC administered to mice and rabbits induced the production of blood-borne IgG antibodies that blocked the infection of human cells by genetically divergent HIV-1 strains from across the world.

"We are backing the research of Dr. Paul's team because his approach using abzymes shows enormous progress in creating an HIV vaccine," said Alan Kleiman, chairman of the board for the Abzyme Research Foundation. "Our foundation aims to drive discovery and innovation in the field of HIV research in hopes of one day eliminating the HIV/AIDS pandemic."

The lead E-VAC was developed from recent proof-of-concept studies that validated targeting of the CD4 binding site and chemical stimulation of the immune system as published recently by Dr. Paul's team in the journals AIDS and The Journal of Biological Chemistry. The work is being conducted at the University of Texas Houston Medical School and California Department of Public Health with support from the National Institutes of Health.

In addition to Dr. Paul, key contributors are Drs. Stephanie Planque, Yasuhiro Nishiyama and Carl Hanson. Dr. Planque is presenting the results at the Vienna AIDS Conference. Dr. Planque's paper was selected by International AIDS Society for the IAS/ANRS Young Scientist Award to be presented at the Conference.

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FDA Approves First Bone Marrow Stimulator to Treat Immune-Related Low Platelet Counts

HHH Note: Congrats to Amgen on this achievement. ITP patients have been waiting a long time. If memory serves correctly, this is the first advancement since the PROSORBA protein A column was introduced some 20 years ago.

The U.S. Food and Drug Administration today approved Nplate (romiplostim), the first product that directly stimulates the bone marrow to produce needed platelets in patients with a rare blood disorder that can lead to serious bleeding.

The condition, which usually develops in adults, is known as chronic immune thrombocytopenic purpura (ITP), a disease that results in a low number of platelets, the blood components that help with clotting. In patients with chronic ITP, the immune system is believed to destroy platelets and the patient's bone marrow is often unable to compensate for this loss.

"This product is important in that it offers a new approach to the treatment of patients with an uncommon blood disorder who are often very ill," said Janet Woodcock, M.D., director, Center for Drug Evaluation and Research, FDA.

The estimated 140,000 people with chronic ITP are prone to bruising and at risk for life-threatening bleeding. Current medical treatment includes corticosteroids and immunoglobulin. Surgery to remove the spleen, a procedure known as a splenectomy, may help some patients. Nplate is approved only for patients with chronic ITP who do not respond sufficiently to current treatments.

FDA based its approval on two randomized clinical trials of about 125 patients who had received at least one prior ITP treatment. One study enrolled patients who still had their spleen, the other enrolled patients who did not.

During six months of treatment, patients who received Nplate had significantly higher platelet counts and maintained those higher counts compared to those who did not receive the drug. The response to Nplate was higher in those patients who still had their spleen than in those patients who had undergone a splenectomy. In those patients who did not receive Nplate, only one experienced a sustained increase in platelet counts.

Safety concerns with Nplate include fibrous deposits in the bone marrow and the possibility that once Nplate is stopped, platelet counts could drop below what they were before beginning treatment.

Additional risks include blood clots due to excessive increases in platelets and, if Nplate were given to patients with an abnormal blood condition known as myelodysplasia, a risk for a form of blood cancer known as acute leukemia. Myelodysplasia, which is associated with low platelet counts, predisposes some patients to leukemia. In a study of 44 patients who had myelodysplasia and received Nplate, four patients developed leukemia. Further clinical trials in patients with predisposing conditions for leukemia will be needed to determine whether the development of leukemia may relate to the use of Nplate. Nplate is approved only for use among patients with chronic ITP.

A Risk Evaluation and Mitigation Strategy (REMS) has been developed to address the risks of Nplate therapy. Under the Food and Drug Administration Amendments Act of 2007, FDA has determined that a REMS is necessary for the benefits of Nplate to outweigh the risks of the product. The REMS will include a Medication Guide for patients and requires that all prescribers and patients enroll in a special program to track the long term safety of Nplate therapy.

Nplate is manufactured by Amgen, Inc. of Thousand Oaks, Calif.

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