Replication deficient human adenovirus vector serotype 19a/64: Immunogenicity in mice and female cynomolgus macaques

TY - JOUR

T1 - Replication deficient human adenovirus vector serotype 19a/64

T2 - Immunogenicity in mice and female cynomolgus macaques

AU - Ragonnaud, Emeline

AU - Schroedel, Silke

AU - Mariya, Silmi

AU - Iskandriati, Diah

AU - Pamungkas, Joko

AU - Fougeroux, Cyrielle

AU - Daradoumis, Joana

AU - Thomsen, Allan R.

AU - Neukirch, Lasse

AU - Ruzsics, Zsolt

AU - Salomon, Michael

AU - Thirion, Christian

AU - Holst, Peter J.

PY - 2018

Y1 - 2018

N2 - The human adenovirus type 19a/64 (hAd19a) is a rare serotype in the human population that transduces human dendritic cells (DCs) and human muscle cells more efficiently than the well-characterized human adenovirus type 5 (hAd5). To further characterize the potential of this vector as a vaccine we designed replication deficient hAd19a, hAd5 and MVA vectors expressing a papillomavirus (PV) antigen fused to the human MHC class II associated invariant chain T cell adjuvant (hIi) and investigated their immunogenicity in vivo in mice and cynomolgus macaques. We initially showed that the hIi encoded in the hAd5 enhanced PV specific CD8+ T cell responses in mice. The T cell responses induced after hAd19a vaccination was similar to those induced by hAd5 vaccination. The hAd19a induced responses were not reduced in presence of preexisting Ad5 immunity in mice. In macaques both vaccines were equally potent at inducing CD8+ T cells after MVA boost, while the level of CD4+ T cell responses were found to be broader in hAd19a primed animals. These data demonstrate the potential of hAd19a as an alternative vector to hAd5 to elicit potent T cell responses to PV.

AB - The human adenovirus type 19a/64 (hAd19a) is a rare serotype in the human population that transduces human dendritic cells (DCs) and human muscle cells more efficiently than the well-characterized human adenovirus type 5 (hAd5). To further characterize the potential of this vector as a vaccine we designed replication deficient hAd19a, hAd5 and MVA vectors expressing a papillomavirus (PV) antigen fused to the human MHC class II associated invariant chain T cell adjuvant (hIi) and investigated their immunogenicity in vivo in mice and cynomolgus macaques. We initially showed that the hIi encoded in the hAd5 enhanced PV specific CD8+ T cell responses in mice. The T cell responses induced after hAd19a vaccination was similar to those induced by hAd5 vaccination. The hAd19a induced responses were not reduced in presence of preexisting Ad5 immunity in mice. In macaques both vaccines were equally potent at inducing CD8+ T cells after MVA boost, while the level of CD4+ T cell responses were found to be broader in hAd19a primed animals. These data demonstrate the potential of hAd19a as an alternative vector to hAd5 to elicit potent T cell responses to PV.

KW - Cynomolgus macaques

KW - Human adenovirus vector

KW - Papillomavirus vaccine

KW - T cell adjuvant

KW - T cell responses

U2 - 10.1016/j.vaccine.2018.07.075

DO - 10.1016/j.vaccine.2018.07.075

M3 - Journal article

C2 - 30190120

AN - SCOPUS:85052725656

SN - 0264-410X

VL - 36

SP - 6212

EP - 6222

JO - Vaccine

JF - Vaccine

IS - 41

ER -