63. A Nonhuman Primate Model for Testing Immuno Gene Therapies for AIDS Using Gene-Protected T Cells

• Published in: Molecular therapy Vol. 11; no. S1; p. S26
• Main Authors: Schmitz, Joern E, Hermann, Felix, Newrzela, Sebastian, Ricketts, Melisa, Schult-dietrich, Patricia, Szyroki, Alexander, Johnson, Robert P, Vonlaer, Dorothee
• Format: Journal Article
• Language: English
• Published: Milwaukee Elsevier Inc 01-05-2005; Elsevier Limited
• Subjects: Acquired immune deficiency syndrome; AIDS; Anthrax; Antigens; Cells; Gene therapy; HIV; Human immunodeficiency virus; Infections; Lymphocytes; Monkeys & apes; Peptides; Vaccines; Vectors (Biology); Italy
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2005.06.091

Peptides derived from the heptad repeat 2 region (HR2) of HIV gp41 (C-peptides) effectively inhibit entry of HIV at the level of virus membrane fusion. A retroviral vector (M87o) expressing a membrane-anchored C-peptide was developed that also has strong antiviral activity in T cell lines and primary T lymphocytes (Egelhofer et al., J.Virol., 2004). M87o was shown to inhibit viral entry more than 10,000-fold in single round infection assays.For testing in nonhuman primates, the M87o vector was adapted to either the SIVmac239 or the SHIV-89.6P C-peptide sequence. The antiviral activity of these constructs against HIV, SIVmac and SHIV-89.6P was analyzed in cell lines and in rhesus PBL. Surprisingly, all three C-peptide types inhibited human as well as the simian viruses. In particular, M87o was highly effective against SIV and SHIV-89.6P and can therefore be tested without modifications in non-human primates. Furthermore, these results indicate that the fusion process is strongly conserved between different lentiviruses.In addition, a protocol for large-scale retroviral transduction of T cells from rhesus macaques was developed. T cells were collected by lymphapheresis, stimulated with anti-CD3 and anti-CD28 immobilized on beads, transduced with GALVenv-pseudotyped M87o and expanded to high cell numbers. This nonhuman primate model will allow optimization as well as safety and efficacy testing of immuno-gene therapy protocols for AIDS.