HIV

Kuan-Teh Jeang of the National Institutes of Health in the U.S. will investigate whether cells infected by one virus become resistant to infection from other viruses, and if this viral interference can confer protection against HIV. The team will develop an attenuated virus to test whether over-expression of viral envelope proteins within cells can confer resistance to further HIV infection.

People born with a genetic mutation in their CCR5 gene are naturally resistant to HIV infection. Philip Gregory of Sangamo BioSciences, Inc. in the U.S. will use zinc finger nuclease technology to specifically disrupt the CCR5 gene as a new strategy to make people resistant to HIV.

Loren Walensky of the Dana-Farber Cancer Institute in the U.S. will apply a new chemical technology to engineer structurally stable HIV-1 antigens for vaccine development. Walensky will test whether preserving the critical biologically active shape of HIV-1 polypeptides will yield neutralizing antibodies upon vaccination with his laboratory's synthetic immunogens.

Bryce Chackerian and David Peabody at the University of New Mexico in the U.S. have developed a new phage display system based on highly immunogenic virus- like particles (VLPs), and will utilize this new system as a platform to identify new vaccines that induce broadly neutralizing antibodies against HIV.

Lynda Morrison of St. Louis University in the U.S. will develop a vaccine vector based on a prototype vaccine for herpes simplex virus 2 (HSV-2) that encodes multiple CD8 T cell epitopes from HIV proteins, and test its ability to stimulate a robust CD8 T cell response against HIV.

One hypothesis of why protective immunity to HIV in the general population is very low is that the virus can exist in a hidden form in the body and can mutate very quickly to escape immune destruction. George Dickson of Royal Holloway University of London will design and evaluate so-called "infinite-epitope" vaccines for their potential to provide simultaneous and broad protective immunity to the many variant forms of HIV.

HIV uses the CCR5 co-receptor protein found in mammals as a major pathway to enter target cells. Because some patients who are exposed, yet resistant, to the virus, or have HIV but do not ever progress to AIDS can exhibit the presence of CCR5 internalizing antibodies, Lucia Lopalco of the San Raffaele Scientific Institute in Italy will attempt to generate "anti-self" antibodies against CCR5 to knock out protein's co-receptor and effectively block HIV entry.

Stephen Kent and John Stambas of the University of Melbourne in Australia will develop and test an attenuated influenza virus vector with an adjuvant that stimulates natural killer cells. The goal of this approach is to induce robust immunity at mucosal surfaces to HIV, which is important in both prevention and control of infection.

Michel Gilbert of the National Research Council Canada will use the single-celled microorganism T. acidophilum to produce HIV proteins with unique sugar residues found only in archaebacteria such as T. acidophilum. By modifying these glycan structures to ones not recognized by humans, Gilbert hopes to elicit a stronger immune response against the virus.

Because HIV infection activates naturally-dormant endogenous retroviruses (ERV) in human cells, Jonah Sacha will target T cells against these ERV antigens. Such targeting to eliminate HIV infected cells could be the basis for new host-directed vaccines. In this project's Phase I research, Sacha and collaborators demonstrated that ERV-specific antibodies are specifically triggered by infection with an exogenous retrovirus like SIV or HIV.