Ovine atadenovirus, a novel and highly immunogenic vector in prime-boost studies of a candidate HIV-1 vaccine.
Ovine adenovirus type 7 (OAdV) is the prototype member of the genus Atadenovirus. No immunity to the virus has so far been detected in human sera. We describe the construction and evaluation of a candidate HIV-1 vaccine based on OAdV and its utilisation alone and in combination with plasmid-, human adenovirus type 5 (HAdV5; a Mastadenovirus)-, and modified vaccinia Ankara (MVA)-vectored vaccines. All vectors expressed HIVA, an immunogen consisting of HIV-1 clade A consensus Gag-derived protein coupled to a T cell polyepitope. OAdV.HIVA was genetically stable, grew well and expressed high levels of protein from the Rous sarcoma virus promoter. OAdV.HIVA was highly immunogenic in mice and efficiently primed and boosted HIV-1-specific T cell responses together with heterologous HIVA-expressing vectors. There were significant differences between OAdV and HAdV5 vectors in priming of naïve CD8(+) T cell responses to HIVA and in the persistence of MHC class I-restricted epitope presentation in the local draining lymph nodes. OAdV.HIVA primed T cells more rapidly but was less persistent than AdV5.HIVA and thus induced a qualitatively distinct T cell response. Nevertheless, both vectors primed a response in mice that reduced viral titres in a surrogate challenge model by three to four orders of magnitude. Thus, OAdV is a novel, underexplored vaccine vector with potential for further development for HIV-1 and other vaccines. The data are discussed in the context of the latest HIV-1 vaccine developments.
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom.
Anne
A
Bridgeman
Yaowaluck
Y
Roshorm
Linda J
LJ
Lockett
Zheng-Zhou
ZZ
Xu
Richard
R
Hopkins
Jan
J
Shaw
Gerald W
GW
Both
Tomás
T
Hanke
D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D046808:Atadenovirus / Q000235:genetics* / Q000276:immunology*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
D016915:AIDS Vaccines