LONDON - PowderJect Pharmaceuticals plc announced results of two studies that it said provide the foundation for clinical trials of a DNA vaccine against HIV. The studies, carried out with simian immunodeficiency virus (SIV), an accepted laboratory model of HIV, demonstrated that DNA vaccination with PowderJect's needleless injection system results in an unprecedentedly high cellular immune response, and indicate that this type of response may protect against infection.

In the first study, in collaboration with the University of Wisconsin and Epimmune Inc., needleless injection of a powdered DNA SIV vaccine elicited the highest T-cell immune response reported to date with a DNA vaccine. The response was equivalent to, and in some cases greater than, that induced by natural infection with SIV. The vaccine consists of a hepatitis B core antigen that acts as an immune system potentiator, fused to DNA encoding a T-cell epitope.

PowderJect, based in Oxford, UK, has filed patents on the use of this fusion concept in DNA vaccination. The study appeared in the May 2000 Journal of Immunology.

Lendon Payne, vice president of research at PowderJect's U.S. vaccines subsidiary, based in Madison, Wis., said, "Potent cellular responses have been observed in HIV-infected individuals who show natural resistance to the virus. These individuals have low viral load and do not develop AIDS as expected. Scientists believe this type of immune response will be an essential component of an HIV vaccine."

The second study, in collaboration with the University of Pittsburgh, showed that powder injection of a DNA vaccine encoding genes from SIV offered protection against SIV transmitted both by injection and by mucosal infection. In the first arm of the study the vaccine reduced the viral load 10- to 10,000-fold following intravenous SIV infection. Although the vaccine did not prevent or eliminate the infection, studies in HIV-infected individuals have shown that reduced viral burden translates into delayed progression to AIDS, and also appears to reduce the risk of transmission.

In the second arm of the study nearly 60 percent of mucosal SIV infections were eliminated within six months. The SIV infection in the study was a variant of the strain used to produce the vaccine, demonstrating for the first time that DNA vaccination offers protection against variants not included in the vaccine.

Designing an effective vaccine against HIV is difficult because the virus continually mutates, generating variants that evade the immune response, and because HIV can be transmitted both by sexual contact and needles. This means an effective vaccine needs to generate immune responses at different sites of entry.

Although this is early stage research, Schaefer Price, president of PowderJect Vaccines Inc., said, "These exciting results show that PowderJect DNA vaccination offers the qualities demanded of an effective vaccine for HIV: protection against different virus variants and two major routes of transmission used by the virus."

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