Epimmune presents SIV vaccine study data showing control of virus despite the presence of viral mutations

Epimmune today presented preliminary data from its ongoing SIV rhesus macaque vaccine study at the AIDS Vaccine 2004 conference in Lausanne, Switzerland.

SIV is the virus equivalent of HIV in many non-human primate species. Preliminary data presented shows that immune responses specific for multiple cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes were induced by the study vaccine and CTL-specific responses were increased by 5- to 10-fold following SIV viral challenge. Five of six vaccinated animals were able to maintain the CTL responses and control viral replication, a measure of vaccine effect, following viral challenge. The control of viral replication occurred despite mutations that are known to contribute to viral escape from the immune system. Unimmunized animals included in the study were not able to control viral replication following SIV challenge.

Study and Vaccine Design The study involves eight animals, six of which were immunized and two of which did not receive the study vaccine. The immunized animals were divided into two groups of three each. Both groups were primed with immunizations at 0, 1, 2 and 3 months with a DNA formulated vaccine followed by a vaccine boost at 8 and 9 months. One group received the DNA formulated vaccine as the boost while the other received a protein-based vaccine as the boost. The animals were then challenged with SIV at month 17. The unimmunized animals were also challenged at the same time. Viral replication, as determined by RNA copies per milliliter (ml) of plasma, is measured periodically for all eight animals.

The study vaccine includes 12 CTL epitopes and four HTL epitopes along with the Company's proprietary, synthetic universal helper T cell epitope, PADRE(R).

Preliminary Study Results Early study results show that both the DNA only and DNA plus protein vaccine regimens induced multiple CTL responses in addition to specific responses to two predicted dominant epitopes. The CTL responses were increased by 5- to 10-fold in the immunized animals following SIV viral challenge which demonstrates the induction of memory CTL that have the capacity to respond quickly and with increased potency to viral infection. These responses were maintained in the immunized animals, but not in the unimmunized animals, following viral challenge. Only the two known dominant epitopes in the test panel were well recognized in control animals and those responses were variable. Previous studies conducted by others have shown that immune responses to only the dominant epitopes were unable to control infection.

Five of six immunized animals controlled viral replication early after infection, as compared to the control animals which did not, with an average of 2.5 logs difference between the vaccinated animals and controls as measured by RNA copies per ml of plasma. Significantly, control of viral replication in the vaccinated animals occurred in the presence of viral mutations, some of which represent CTL escape mutants. It has been shown previously that one mechanism by which the virus is able to replicate in high numbers is escape of immune control due to mutations in viral epitope sequences.

Dr. Mark Newman, Vice President, Research and Development of Epimmune said, "These preliminary results, in a non-human primate model, provide further support for our multi-epitope approach. The fact that the immunized animals have been able to maintain the CTL responses compared to the control animals which have not, particularly in the presence of escape mutants, gives us confidence we are on the right track with our vaccine product development."