Objective
The initial goal of the Concerted Action was to evaluate FIV as a model for HIV and AIDS. Initially several aspects of FIV biology were investigated. As a result the Concerted Action began to focus on vaccinerelated issues. The aim in this area was to define the mechanisms by which vaccines produced protective immunity. These studies should suggest strategies for the development of vaccines against HIV.
Research focuses on feline immunodeficiency virus (FIV) as a model for human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) with special emphasis on using the model to develop vaccines and test antiviral drugs. In fact an effective vaccine against FIV already exists, but because it is derived from infectious material, the same approach can probably not be applied to humans. The participants' aim is to clone and express whole or partial viral proteins, with a view to incorporating these into vaccines. The multicentre approach is particularly useful here, as there appear to be several different viruses and it is important to ensure that as many viruses as possible are available to challenge vaccinated cats. Another collaborative venture involves developing assays to detect FIV infection in living cats and in the test tube, and to monitor the animals' immune response to the virus. The work has already produced a virus neutralisation test.
Feline immunodeficiency virus (FIV) has proved to be an analogue of human immunodeficiency virus (HIV) and a useful model for developing vaccines against acquired immune deficiency syndrome (AIDS). In cats protection has been achieved by Yamamoto et al using chemically inactivated virus or virus infected cells. While this approach demonstrates the important point that vaccination is feasible, the use of antigen derived from infectious material is probably not feasible for HIV vaccine development.
The approach taken by participating laboratories in the concerted action has been to work towards the use of recombinant proteins of the virus, particularly the products of the env gene, as immunogens in vaccines. Several prototype FIV strains have been molecularly cloned and proteins have been expressed in a number of different systems. Some of these are presently being tested in vaccine trials. A database of sequences of the env gene of many European isolates has been established and virus neutralization patterns between strains have been investigated. Hence it will be possible to choose genetically and antigenetically and similar and distinct strains of FIV for use as challenge viruses in protection trials.
There has been considerable collaboration in the development of assays to detect FIV infection in vivo and in vitro, and to monitor the serological responses to the virus. Monoclonal antibodies have been produced to the major structural proteins of the virus and are available for use by all participating groups.
A major conclusion of the work of the collaborating centres was that FIV is an excellent model for studying various aspects of lentiviral biology that the virus shares with HIV. Of particular interest was the pathogenesis of infection and the dynamics of viral growth and the resulting immune response in infected individuals. The differences that were found between the biology of FIV and HIV emphasize the common pathways by which the 2 viruses achieve essentially identical final results in their target species. The second major conclusion was that the model was most valuable in developing strategies for vaccination. The development of a successful vaccine based on inactivated virus provided an excellent opportunity to define the determinants of protective immunity.
Funding Scheme
CON - Coordination of research actionsCoordinator
G61 1QH Glasgow
United Kingdom