Evaluation of a self-inactivating lentiviral vector expressing simian immunodeficiency virus gag for induction of specific immune responses in vitro and in vivo.
Humoral and cellular immune responses have been shown to play a fundamental role in controlling simian and/or simian-human immunodeficiency virus (SIV-SHIV) replication in infected macaques. Therefore, the appropriate induction of both compartments of the immune system should be elicited after immunization. In this context, viral vectors have been proven effective in inducing both humoral and cellular immune responses during immunization protocols after direct injection in vivo. Among them, recombinant self-inactivating lentiviral vectors represent a useful strategy for vaccine development because they efficiently transduce and express foreign genes into a wide variety of mammalian cells. Here we report on the development and evaluation of a self-inactivating HIV-based lentiviral vector expressing a codon-optimized SIV Gag sequence (TY2-SIVGagDX), which when used to transduce dendritic cells mediated in vitro expansion of Gag-specific T cells derived from an SHIV-infected cynomolgus monkey, as measured by interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) and (51)Cr release standard assays. To evaluate the ability to elicit specific immune responses in vivo, TY2-SIVGagDX was also employed in a vaccination protocol after a single intramuscular injection in BALB/c mice. Results indicated that the vector was able to efficiently induce both cellular and humoral responses, as measured by IFN-gamma ELISPOT assay and antibody production. These data further confirm that lentiviral vectors encoding viral genes represent an advantageous delivery system for vaccine development.
Buffa
Viviana
V
National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
Negri
Donatella R M
DR
Leone
Pasqualina
P
Borghi
Martina
M
Bona
Roberta
R
Michelini
Zuleika
Z
Compagnoni
Daniela
D
Sgadari
Cecilia
C
Ensoli
Barbara
B
Cara
Andrea
A
D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics; D007114:Immunization; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D016086:Lentivirus / Q000235:genetics*; D007963:Leukocytes, Mononuclear; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015683:Gene Products, gag; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma