Simian and feline immunodeficiency viruses: animal lentivirus models for evaluation of AIDS vaccines and antiviral agents

Abstract

Infection of captive macaques with simian immunodeficiency virus (SIV) and domestic cats with feline immunodeficiency virus (FIV), both discovered in the last five years, represent excellent animal models for infection of humans with the human immunodeficiency virus (HIV). Protection against challenge infection and protection against development of simian and feline acquired immunodeficiency syndrome has been achieved in each model by use of inactivated whole virus or virus-cell vaccines. A recombinant SIV envelope peptide vaccine has also proved efficacious. These vaccines have protected against 10-100 animal infectious doses of the homologous cell-free virus given systemically, and, in the simian model, apparently show cross protection against a heterologous strain of SIV. Protected animals appear free of any latent infection although late breakthroughs of infection in a few animals imply that not all vaccinated animals are completely protected. The mechanism of protection in the simian model apparently involves envelope antibody but the role of neutralizing antibody remains unclear. Questions remaining to be answered in both SIV and FIV models are: (1) the duration of immunity, (2) the extent of protection against heterologous strains and mucosal infection, (3) protection against infection with cell-associated virus and (4) the role, if any, of cellular immunity in vaccine protection. Initial attempts at post-infection immunotherapy with SIV vaccines have not yet been successful. The inactivated whole SIV and FIV vaccines offer a promising start and provide hope that a prophylactic AIDS vaccine will be developed. Use of these animal models for antiviral therapy is just now getting underway. Both models should prove especially useful for studies of prophylaxis and therapy, especially during the early stages of infection and for investigations on drug pharmacokinetics or toxicity that can not be done as well in HIV-infected humans. The animals will also be ideal for testing the pathogenicity of drug-induced mutant forms of SIV and FIV. For these purposes it will be necessary to create self-sustaining specific pathogen-free macaque and cat breeding colonies and provide increased housing facilities for infected animals. The future of AIDS research is crucially dependent on the long term availability of these animal models.