Antigen-presenting Cell-targeted Lentiviral Vectors Do Not Support the Development of Productive T-cell Effector Responses: Implications for in Vivo Targeted Vaccine Delivery

Overview

Journal Gene Ther

Date 2017 May 26

PMID 28540936

Citations 8

Authors

C Goyvaerts

Y De Vlaeminck

D Escors

S Lienenklaus

M Keyaerts

G Raes

K Breckpot

Affiliations

Soon will be listed here.

Abstract

Targeting transgene expression specifically to antigen-presenting cells (APCs) has been put forward as a promising strategy to direct the immune system towards immunity. We developed the nanobody-display technology to restrict the tropism of lentiviral vectors (LVs) to APCs. However, we observed that immunization with APC-targeted LVs (DC2.1-LVs) did not evoke strong antigen-specific T-cell immunity when compared to immunization with broad tropism LVs (VSV.G-LVs). In this study, we report that VSV.G-LVs are more immunogenic than DC2.1-LVs because they transduce stromal cells, which has a role in activating antigen-specific T cells. Moreover, VSV.G-LVs trigger a pro-inflammatory innate immune response through transduction of APCs and stromal cells, while DC2.1-LVs trigger a type I interferon response with anti-viral capacity. These findings question the rationale of targeting LVs to APCs and argue for the development of VSV.G-LVs with an improved safety profile.

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