Nonintegrating Lentivector Vaccines Stimulate Prolonged T-Cell and Antibody Responses and Are Effective in Tumor Therapy

Abstract

؉ T-cell and antibody responses to the secreted hepatitis B virus (HBV) surface antigen expressed from a nonintegrating lentivector injected intramuscularly. The induction, specificity, and kinetics of antibody production closely mimicked those of natural HBV infection. In this case, both the vector genome and the immune response were maintained for at least 2 months. Together, our data indicate that nonintegrating lentivectors can be employed to generate effective vaccines.

Lentiviral Vectors in Immunotherapy

“…Lentivectors have been extensively used in vaccination protocols, due to their capacity of raising strong transgene-specific immune responses [9,17,30,[38][39][40]. Interestingly, some reports suggest that lentivectors are incapable of inducing DC maturation in vitro, suggesting that some components of the lentivector preparations provide signals 2 and 3 through a mechanisms not well understood [40,41].…”

“…Interestingly, although a full DC maturation phenotype was not achieved ex vivo, coexpression of these MAPK activators with an OVA-containing transgene or MELAN-A induced significant antigen-specific CD4 and CD8 T cell responses. Moreover, these lentivectors improved survival in a murine tumour model for lymphoma, both with integrating and non-integrating lentivectors [38]. Other molecules have been applied for DC maturation.…”

“…In fact, vFLIP expression has resulted to be a strong adjuvant when expressed in DCs, leading to strong DC maturation and effective CD4 and CD8 T cell responses. Lentivector expression of vFLIP significantly improves anti-tumour activities in a lymphoma mouse model and anti-parasitic efficacy in an OVA-expressing leishmania model [38,54]. Lentivectors have also been used to inhibit negative regulators of NF-κB activation, such as the ubiqutin ligase A20.…”

“…These modified DCs induced strong activation and proliferation of antigen-specific T cells. [17,[33][34][35][36][37][38].…”

A Protocol for the Production of Integrase-deficient Lentiviral Vectors for CRISPR/Cas9-mediated Gene Knockout in Dividing Cells

“…Furthermore, the efficacy of IDLVs in cancer immunotherapy and as a means of inducing protective immune responses to human pathogens has been characterized in different experimental settings. [38][39][40] The ability to simultaneously deliver Cas9 and sgRNA through a single vector enables facile and robust in vivo gene editing, which is particularly advantageous for developing a translatable gene therapy products (reviewed in Maeder and Gersbach 42 ). In the current manuscript, we aimed to establish an all-in-one IDLV-CRISPR/Cas9 system for efficient gene editing in vitro and in vivo.…”