First Author | Lopez J | Year | 2022 |
Journal | Cell Rep | Volume | 40 |
Issue | 4 | Pages | 111142 |
PubMed ID | 35905717 | Mgi Jnum | J:332425 |
Mgi Id | MGI:7329689 | Doi | 10.1016/j.celrep.2022.111142 |
Citation | Lopez J, et al. (2022) A lentiviral vector encoding fusion of light invariant chain and mycobacterial antigens induces protective CD4(+) T cell immunity. Cell Rep 40(4):111142 |
abstractText | Lentiviral vectors (LVs) are highly efficient at inducing CD8(+) T cell responses. However, LV-encoded antigens are processed inside the cytosol of antigen-presenting cells, which does not directly communicate with the endosomal major histocompatibility complex class II (MHC-II) presentation pathway. LVs are thus poor at inducing CD4(+) T cell response. To overcome this limitation, we devised a strategy whereby LV-encoded antigens are extended at their N-terminal end with the MHC-II-associated light invariant chain (li), which contains an endosome-targeting signal sequence. When evaluated with an LV-encoded polyantigen composed of CD4(+) T cell targets from Mycobacterium tuberculosis, intranasal vaccination in mice triggers pulmonary polyfunctional CD4(+) and CD8(+) T cell responses. Adjuvantation of these LVs extends the mucosal immunity to Th17 and Tc17 responses. A systemic prime and an intranasal boost with one of these LV induces protection against M. tuberculosis. This strategy improves the protective power of LVs against infections and cancers, where CD4(+) T cell immunity plays an important role. |