Development and use of SIV-based Integrase defective lentiviral vector for immunization.

Abstract

Integrase (IN) defective lentiviral vectors have a high safety profile and might prove useful as immunizing agents especially against HIV-1. However, IN defective SIV-based vectors must be developed in order to test their potential in the non-human primate models (NHP) of AIDS. To this aim we tested a novel SIV-based IN defective lentiviral vector for its ability to induce sustained immune responses in mice. BALB/c mice were immunized once intramuscularly with a SIV-based IN defective lentiviral vector expressing the model antigen enhanced green fluorescence protein (eGFP). Immune responses were evaluated 90 days after the injection and compared with those elicited with the IN competent counterpart. The IN defective vector was able to efficiently elicit specific and long-lasting polyfunctional immune responses as evaluated by enzyme-linked immunospot (ELISPOT) assays for interferon-gamma (IFN-gamma) in spleens, bone marrow (BM) and draining lymph nodes, and by intracellular staining (ICS) for IFN-gamma, Interleukin-2 (IL-2) and tumor necrosis factor (TNF-alpha) in both splenocytes and BM cells without integration of the vector into the host genome. This is the first demonstration that an IN defective SIV-based lentiviral vector provides effective immunization, thus paving the way for the construction of IN defective vectors expressing SIV antigen(s) and test their efficacy against a SIV virus challenge in the NHP model of AIDS.

• Authors: Zuleika Michelini, Donatella R M Negri, Silvia Baroncelli, Massimo Spada, Pasqualina Leone, Roberta Bona, Mary E Klotman, Andrea Cara
• Journal: Vaccine (Vaccine) Vol. 27 Issue 34 Pg. 4622-9 (Jul 23 2009) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 19523909 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin G
• Interleukin-2
• SAIDS Vaccines
• Tumor Necrosis Factor-alpha
• Viral Nonstructural Proteins
• enhanced green fluorescent protein
• Green Fluorescent Proteins
• Interferon-gamma
• Integrases

Topics

• Animals
• Bone Marrow (immunology)
• Female
• Genes, Reporter
• Genetic Vectors
• Green Fluorescent Proteins (genetics, immunology)
• Immunoglobulin G (blood)
• Integrases (deficiency)
• Interferon-gamma (biosynthesis)
• Interleukin-2 (biosynthesis)
• Leukocytes, Mononuclear (immunology)
• Lymph Nodes (immunology)
• Mice
• Mice, Inbred BALB C
• SAIDS Vaccines (genetics, immunology)
• Simian Immunodeficiency Virus (genetics, immunology)
• Spleen (immunology)
• Tumor Necrosis Factor-alpha (immunology)
• Viral Nonstructural Proteins (deficiency)