Humoral Responses Elicited by Adenovirus Displaying Epitopes Are Induced Independently of the Infection Process and Shaped by the Toll-Like Receptor/MyD88 Pathway

Frontiers in Immunology

Bernhard Ryffel²  Ronan Le Goffic³  Patrick Perrieau⁴  Lena Zig⁴  Najat Raddi⁴  Aleksandra Anchim⁴  Karim Benihoud⁴ 

[1] Experimental and Molecular Immunology and Neurogenetics, UMR 7355, CNRS-University of Orléans, Orléans, France;Institute of Infectious Diseases and Molecular Medicine (IDM), Cape Town, South Africa;VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France;Vectorologie et thérapeutiques anticancéreuses, UMR 8203, CNRS, Univ. Paris-Sud, Gustave Roussy, Université Paris-Saclay, Villejuif, France;

关键词: adenovirus;    fiber;    innate immunity;    antibody isotype;    MyD88;    mitochondrial antiviral-signaling;   

DOI  :  10.3389/fimmu.2018.00124

来源: DOAJ

【 摘 要 】

The use of serotype 5 adenovirus (Ad)-derived vectors in vaccination is confronted to preexisting anti-Ad immunity. Epitope display on Ad capsid is currently being investigated as an alternative approach of vaccination. The present study seeks to better understand virus- and host-related factors controlling the efficacy of this new vaccination approach. In contrast to an Ad vector expressing ovalbumin as a transgene, Ad displaying an ovalbumin-derived B-cell epitope inserted into the fiber protein was able to elicit antibody responses in both Ad-naive and Ad-immune mice. Moreover, introduction of a set of mutations abrogating Ad interaction with its receptors did not modify the virus capacity to elicit a humoral response against the inserted epitope while reducing its capacity to mount antibody responses against the transgene product. Taken as a whole these data indicate that the efficacy of Ad displaying epitopes requires neither Ad binding to its receptors nor the infection process. In addition, the use of genetically deficient mice demonstrated that both toll-like receptor (TLR)/MyD88 and RIG-I/mitochondrial antiviral-signaling (MAVS) innate immunity pathways were dispensable to mount anti-epitope antibody responses. However, they also revealed that TLR/MyD88 pathway but not RIG-I/MAVS pathway controls the nature of antibodies directed against the displayed epitope.

【 授权许可】

Unknown