Naslov
MCMV expressing high affinity NKG2D ligand MULT- 1: a model vaccine for congenital CMV infection

Autori
Hiršl, Lea ; Kveštak, Daria ; Brizić, Ilija ; Jenuš, Juranić Lisnić, Vanda ; Krmpotic, Astrid ; Jonjic, Stipan

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

Skup
The 17th Meeting of the Society for Natural Immunity

Mjesto i datum
San Antonio (TX), Sjedinjene Američke Države, 28.05.2018. - 01.06.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV, NK cells, CD8 T cells, NKG2D, congenital infection

Sažetak
Cytomegaloviruses (CMVs) encode numerous non- essential immunoevasive genes which can be deleted or replaced by any other gene without affecting viral growth or fitness in vitro. However, the deletion of viral immunoevasins attenuates the virus in vivo, thus enabling the generation of various viruses with altered virulence. We have previously shown that murine CMV (MCMV) expressing RAE-1γ (one of the cellular ligands for the NKG2D receptor) is highly attenuated in vivo but despite the attenuation retains the capacity to induce strong adaptive immune response to viral and vectored antigens. Here we demonstrate that a recombinant MCMV expressing high affinity NKG2D ligand MULT-1 is dramatically attenuated in vivo by NK cells in a NKG2D-dependent manner in adult immunocompetent mice as well as in immunologically immature newborns. MULT-1MCMV was controlled more rapidly compared to RAE-1γMCMV and failed to reach the brain of infected newborn mice. As a result, newborn mice infected with this virus were devoid of brain inflammation and microglia polarization induced by a congenital CMV infection. Despite being highly sensitive to NK cell control, MULT-1MCMV induced an efficient CD8+ T cell response in both adult and newborn mice. Similarly to RAE-1γ MCMV, in vitro studies have shown that MULT-1 expressing virus provides a strong costimulation of T cells apparently overcoming viral evasion of other costimulatory signals. Altogether, we provide evidence for a dual function of NKG2D ligand MULT-1 expressed by MCMV:in provoking a strong NK cell control as well as augmenting the T cell response. This study provides additional evidence that CMV expressing NKG2D ligands possesses characteristics which makes it a very promising candidate to be used as a vaccine vector.

Izvorni jezik
Engleski

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