PR Newswire - November 15, 1995

The phase I trial with HGP-30 will evaluate safety and HIV-1 directed immune responses in HIV infected individuals. The trial will include 22 HIV patients with CD4 counts between 50 and 600. Each patient will receive three immunizations of the HGP-30 HIV immunogen during the course of six months. Previous clinical phase I studies with HGP-30 in 38 non-infected volunteers have already been successfully concluded in the United Kingdom and California.

The clinical trial will be conducted by AIDS RESEARCH Alliance, a non-profit AIDS research organization located in West Hollywood, California. AIDS patients in the Los Angeles area who wish to know whether they are eligible to participate in the HGP-30 clinical trials may contact AIDS RESEARCH Alliance at 310-358-2423.

Gregory Britt, Chief Executive Officer of AIDS RESEARCH Alliance, stated, "Effective strategies for augmenting the body's own immune responses to HIV infection are desperately needed. We believe that HGP-30 represents a rational approach for accomplishing that goal. AIDS RESEARCH Alliance is proud to be the clinical site for this project."

Geert Kersten, Chief Executive Officer of CEL-SCI, stated, "We have been long-term believers in the powers of the immune system. We now seek to marshal the strength of the immune system against a constant piece of the HIV virus with the goal of slowing or stopping the progression of HIV infection to AIDS."

Rights to the HGP-30 technology are owned by Viral Technologies, Inc., a 100% owned subsidiary of CEL-SCI Corporation.

CEL-SCI Corporation has pioneered the development of Multikine(TM) for treatment of cancers and other immunodeficiency diseases.

SCIENTIFIC BACKGROUNDER ON HIV THERAPEUTIC VACCINE, HGP-30

Background: The development of AIDS among homosexuals, heterosexuals, hemophiliacs and intravenous drug abusers has become a global problem. It is estimated that approximately 15 million individuals are infected with HIV worldwide and by the year 2000 this number could reach 40 million. Therefore, it is important to develop vaccines that can be used to prevent infection and help boost immune response in HIV infected individuals so as to be able to slow or arrest the progression of disease. Studies with HGP-30: CEL-SCI Corporation, through its subsidiary Viral Technologies, Inc., is involved in the development of an HIV-1 core based synthetic peptide vaccine, HGP-30, that has an amino acid sequence based on a highly conserved antigenic region of p17. This antigen was chosen since the presence of antibodies to HIV-1 p17 epitopes has been shown to correlate with HIV infection and disease progression. Recent studies have shown that the immunosuppressive effect of HIV proteins can be reversed by antibodies to p17.

HGP-30 is a 30 amino acid synthetic peptide which contains T and B cell epitopes, along with the CTL (cytotoxic T-cell) epitope. It is coupled to KLH (Keyhole Limpet Hemocyanin) as a carrier and administered with alum as an adjuvant. The sequence of the region of p17 represented by HGP-30 is fairly well conserved among different HIV-1 strains from different parts of the world.

Immunological studies in several animal species including mice, rabbits, monkeys and chimpanzees demonstrated that the HGP-30 vaccine is well tolerated in the different animal species and elicits antibody and cellular proliferative responses. Subsequently, phase 1 clinical trials were carried out in the U.K. and U.S.A.

Immune Responses Observed in HGP-30 Immunized Subjects: Analyses of the sera from HGP-30 vaccinees showed that a large number of the immunized subjects developed antibodies to HGP-30. The vaccine preparation was well tolerated by the vaccinees.

Analyses of the peripheral blood mononuclear cells from HGP-30 immunized subjects were performed to measure antigen specific immune cellular proliferation responses. The numbers of vaccines that developed cytotoxic T-cell and lymphoproliferative responses were higher in the lower dose groups (10 and 25 mcg/kg) than in the higher dose groups (50 and 100 mcg/kg). Based on these results, a dose of 25 mcg/kg of the vaccine has been selected for initial evaluation of the safety and immune response to HGP-30 in HIV infected individuals. The CTL response has been shown to be CD8+ and is inhibited by a CD8+ specific antibody. CD8+ CTL activity is considered to be necessary for the clearance of virus infected cells.

HIV Virus Challenge Studies: A number of investigators have used the SCID-human PBL mouse model to evaluate the effect of drugs and vaccines in affording protection against HIV virus challenge in SCID mice reconstituted with peripheral blood mononuclear cells from subjects undergoing AZT treatment or immunization with HIV vaccine candidates. In a pilot experiment, cells from an HGP-30 immunized volunteer were examined for their ability to protect mice against HIV-1 infection by infectious HIV challenge as compared to cells from a normal donor. Groups of SCID mice were reconstituted with 2 x 10(7) cells from a vaccinee or a normal donor and challenged with a 10,000 TCID50 dose of HIV-1 (Lai). In the group of SCID mice that were reconstituted with leukocytes from an HGP-30 vaccinee, there was increased protection from infection as compared to the group of mice that received leukocytes from a normal donor. These results suggest that leukocytes from an HGP-30 vaccinee have developed some protective, cell mediated immune responses against HIV-1 infection.

In order to evaluate if CD8+ cells were responsible for the increased protection, SCID mice were reconstituted with cells after depletion of CD8+ cells, either from a normal donor or an HGP-30 vaccinee. The increased protection from HIV infection observed with SCID mice reconstituted with total leukocytes from the vaccinated subject dropped to that observed with cells from a normal donor after removal of CD8+ cells. These results confirm earlier observations which showed that the protective CTL responses developed in the HGP-30 vaccinees are due to CD8+ cells.

The HIV-1 strain used for these virus challenge studies was HIV-Lai, whereas the HGP-30 sequence is analogous to the HIV-SF2 strain. These results suggest that it is possible to develop protection against other virus strains of the same clade. Both HIV-Lai and HIV-SF2 belong to the B clade of HIV-1. The high degree of conservation in other clades of the region of HIV-1 p17 represented by HGP-30 suggests that a HGP-30 based vaccine may be useful in immunotherapy of HIV infected individuals from different regions of the world.

Current and Future Clinical Studies: The HGP-30 vaccine preparation is currently being evaluated in vaccinees previously immunized with HGP- 30. This study is designed to determine if the cells of previously immunized vaccinees have memory cells that can be stimulated with booster immunizations. Two booster shots with the vaccine have been given and humoral and cellular immune responses will be evaluated by measuring antibody titers and HGP-30 specific cell proliferation responses. In addition, blood cells from some of the vaccinees will be evaluated in SCID mice to determine if the SCID mice reconstituted with cells from immunized subjects are protected from challenge with infectious HIV-1.

A study with HGP-30 vaccine in HIV infected individuals has just been cleared to proceed in California. This study will evaluate the safety and the stimulation of humoral and cellular immune responses with the vaccine in HIV infected subjects and is designed to indicate if immunization with the HGP-30 vaccine preparation affects disease markers.

Conclusion: A vaccine to be used for prevention or for immunotherapy should be able to reconstitute both humoral and cellular immune responses. Studies to date with the HIV-1 p17 synthetic peptide vaccine preparation (HGP-30) in healthy non-infected volunteers have shown that it is possible to elicit both humoral and cell mediated immune responses to HGP-30.

CONTACT: Gregory Britt, chief executive officer of AIDS RESEARCH Alliance, 310-358-2423; or Geert Kersten, chief executive officer of CEL-SCI, 703-549-5293/ 08:31 EST

Copyright (c) 1995/PR NewsWire. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Permissions Desk, PR Newswire, 810 Seventh Avenue, New York, NY 10019.
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