Successful immunization with a single injection of non-integrating lentiviral vector.
We evaluated the ability of an integrase (IN)-defective self-inactivating lentiviral vector (sinLV) for the delivery of human immunodeficiency virus-1 (HIV-1) envelope sequences in mice to elicit specific immune responses. BALB/c mice were immunized with a single intramuscular injection of the IN-defective sinLV expressing the codon optimized HIV-1(JR-FL) gp120 sequence, and results were compared with those for the IN-competent counterpart. The IN-defective sinLV elicited specific and long-lasting immune responses, as evaluated up to 90 days from the immunization by enzyme-linked immunosorbent spot (ELISPOT) and intracellular staining (ICS) for interferon-gamma (IFN-gamma) assays in both splenocytes and bone marrow (BM) cells, chromium release assay in splenocytes, and antibody detection in sera, without integration of the vector into the host genome. These data provide evidence that a single administration of an IN-defective sinLV elicits a significant immune response in the absence of vector integration and may be a safe and useful strategy for vaccine development.
Negri
Donatella R M
DR
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Michelini
Zuleika
Z
Baroncelli
Silvia
S
Spada
Massimo
M
Vendetti
Silvia
S
Buffa
Viviana
V
Bona
Roberta
R
Leone
Pasqualina
P
Klotman
Mary E
ME
Cara
Andrea
A
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D003673:Defective Viruses / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007273:Injections, Intramuscular; D019426:Integrases / Q000235:genetics; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D013997:Time Factors
D015699:HIV Envelope Protein gp120; D019426:Integrases