Naslov
RAE-1γ expressed by recombinant herpesvirus dramatically improves its vector capacity and promotes specific immune response

Autori
Tršan, Tihana ; Busche, Andreas ; Abram, Maja ; Babić Čač, Marina ; Golemac, Mijo ; Tomić, Adriana, Krmpotić, Astrid ; Messerle, Martin ; Jonjić, Stipan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
The 13th meeting of the Society for Natural Immunity NK2012 / - , 2012

Skup
The 13th meeting of the Society for Natural Immunity NK2012

Mjesto i datum
Pacific Grove (CA), Sjedinjene Američke Države, 20.04.2012. - 24.04.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV; CMV vaccine vector; NKG2D; CD8 T cell vaccine
(CMV; CMV vaccine vector; NKG2D; CD8 T cell vaccine)

Sažetak
INTRODUCTION. NKG2D is a potent activating receptor expressed by cells of innate and adaptive immunity that recognizes cell surface molecules structurally related to MHC-I proteins induced by infection or other type of cellular stress. Engagement of NKG2D leads to cytotoxicity and cytokine secretion by NK cells, or to costimulation of CD8+ T cells. Both human and mouse cytomegalovirus (CMV) developed numerous evasive mechanisms to prevent expression of NKG2D ligands. We have recently shown that insertion of the gene encoding NKG2D ligand in the place of its viral inhibitor is a powerful approach for engineering immunologically attenuated viruses (Slavuljica et al., JCI 2010). Here we present the ability of such recombinant virus to serve as a vaccine vector able to promote robust and protective CD8+ T cell response to various pathogens. METHODS AND RESULTS. On the backbone of MCMV expressing RAE-1 we constructed recombinant viruses bearing immunodominant CD8+ T cell epitopes such as listeriolysin (LLO) of Listeria monocytogenes or SIINFEKL peptide derived from ovalbumin. These epitopes were introduced in the place of MCMV CD8+ T cell epitope m164 by orthotopic peptide swap method (Lemmermann et al., 2011). The recombinant viruses were tested for their capacity to activate NK cells and to induce specific memory CD8+ T cell response. Although extremely attenuated, MCMV expressing RAE1 and foreign epitope induced a strong and long-lasting CD8+ T cell response able to protect immunized mice against bacterial challenge infection. CONCLUSIONS. Our results demonstrated that herpesviruses engineered to express NKG2D ligand in addition to a foreign CD8+ T cell epitope dramatically improved efficacy and longevity of the protective CD8+ T cell response, suggesting that a similar approach could be used in designing new vaccine vectors.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA