Simian immunodeficiency viruses (SIV) are a group of primate retroviruses that are morphologically and antigenically related to human immunodeficiency, viruses (HIVs). HIV infection in humans is associated with the development of Acquired Immune Deficiency Syndrome (AIDS). The SIV group includes strains isolated from macaques (SIV.sub.mac) (see, e.g., Daniel et al., Science 228, 1201 (1985)); sooty mangabey monkeys (SIV.sub.smm) (see, e.g., Lowenstein et al., Int. J. Cancer 38, 563-574, (1986)); African Green Monkeys (SIV.sub.agm)(see, e.g., Otha et al., Int. J. Cancer 41, 115 (1988)); chimpanzees (SIV.sub.cpz-ant) (PCT application WO 91/19785 published 26 Dec. 1991) and mandrills (SIV.sub.mnd)(Tsujimoto et al., J. Virol. 62, 4044 (1988)). Macaques infected with cultured SIV develop opportunistic infections and other manifestations of immunodeficiency associated with a loss of CD4+ cells.
Both HIV and SIV replicate in vitro in a variety of CD.sub.4 + cell lines and in primary cell cultures. Cellular infection causes drastic cytopathic effects and cytolysis. The cytopathic effects include syncytia formation, which is produced by the interaction of viral envelope glycoproteins (expressed on the surface of the infected cells) and uninfected cells that express CD.sub.4.
HIV and SIV can also establish persistent infections in vitro. See, e.g., Benveniste et al., J. Med. Primatol., 19, 351 (1990); Lairmore et al. , Arch. Virol. 121, 43 (1991). Persistently infected cells can produce infectious as well as defective virus particles. HIV mutants defective in the pol region have been obtained from cultures. Folks et al., Science, 231, 601 (1986). Products of the pol virus genome region, including the virus protease enzyme, are required for viral infectivity. See, e.g., Henderson et al., J. Virol., 66, 1856 (1992); Henderson et al., J. Med. Primatol. 19, 411 (1990). A noninfectious HIV mutant able to synthesize all major viral proteins except proteins p64 and p34 is disclosed in U.S. Pat. No. 4,752,565 to Folks et al. A non-infectious mutant HIV virus lacking a functional protease, and a cell line infected with the mutant virus, is described in Benveniste et al., J. Med. Primatol., 19, 351 (1990). Mutant SIV strains producing large amount of either the envelope glycoprotein gp120 or the nucleic acid binding gag protein are described in Benveniste et al., J. Med. Primatol., 19, 351 (1990).
Additionally, a natural SIV isolated from chimpanzees has been reported as having antigenic properties closer to HIV-1 than HIV-2, and has been proposed for use in preparing antibodies for diagnostic kits and for developing vaccines against HIV-1. Published application, WPI Ace No: 90-329700/44.
Various strategies are currently being investigated in attempts to develop effective vaccines against retroviruses such as SIV and HIV, including subunit vaccines and live recombinant virus vaccines. Synthetic peptides containing multiple epitopes of a given pathogen are also under investigation for use in vaccines. See, e.g., PCT patent application WO 91/05864, international publication date 2 May 1991.
Inactivated whole-virus vaccines consist of purified preparations of intact viral particles that have been rendered non-infectious by chemical or physical methods. Inactivated SIV viral vaccines have been tested in macaques, and have resulted in the development of high levels of neutralizing antibodies. Johnson et al., Proc. Natl. Acad. Sci. USA, 89, 2175 (1992). While such vaccines are comparatively easy to produce and contain most or all of the important immunological epitopes, production of these vaccines requires the propagation of large amounts of infectious virus. Additionally, the virus must be rendered completely non-infectious without altering various immunological epitopes.
Because both SIV and HIV are spread by contaminated body fluids, immunochemical testing of sera can be used to determine whether animals or humans are infected with SIV or HIV. Immunochemical techniques employ proteins isolated from purified virus particles or infected cell lysates as antigens to detect serum antibodies directed against the virus of interest. These antigens may also be used in competition studies designed to detect the presence of viral antigens. Preparation of the viral proteins requires manipulating large volumes of virus and tissue cultures; if the virus is infectious workers are exposed to a risk of accidental infection.