VACCINE PROPERTIES OF RECOMBINANT HERPESVIRUS EXPRESSING LIGAND FOR NKG2D RECEPTOR (CROSBI ID 569232)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Stipan Jonjić
engleski
VACCINE PROPERTIES OF RECOMBINANT HERPESVIRUS EXPRESSING LIGAND FOR NKG2D RECEPTOR
Human CMV (HCMV) is a major cause of morbidity and mortality in both congenitally infected and immunocompromised individuals. Development of an effective HCMV vaccine would help protect these vulnerable groups. NK group 2, member D (NKG2D) is a potent activating receptor expressed by cells of the innate and adaptive immune systems. Its importance in HCMV immune surveillance is indicated by the elaborative evasion mechanisms evolved by the virus to avoid NKG2D. In order to study this signaling pathway, we engineered a recombinant mouse CMV expressing the high-affinity NKG2D ligand RAE-1γ (RAE-1γMCMV). Expression of RAE-1γ by MCMV resulted in profound virus attenuation in vivo and lower latent viral DNA loads. RAE-1γMCMV infection was efficiently controlled by immunodeficient hosts, including mice lacking type I interferon receptors or immunosuppressed by sublethal γ-irradiation. Features of MCMV infection in neonates were also diminished. Despite tight innate immune control, RAE-1γMCMV infection elicited strong and long-lasting protective immunity. Maternal RAE-1γMCMV immunization protected neonatal mice from MCMV disease via placental transfer of antiviral Abs. Despite strong selective pressure, the RAE-1γ transgene did not exhibit sequence variation following infection. Together, our results indicate that use of a recombinant virus encoding the ligand for an activating NK cell receptor could be a powerful approach to developing a safe and immunogenic HCMV vaccine.
VACCINE PROPERTIES; NKG2D; RECOMBINANT HERPESVIRUS
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Podaci o prilogu
2010.
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Podaci o matičnoj publikaciji
Podaci o skupu
Annual Meeting of the Austrian Society for Allergology and Immunology 2010
pozvano predavanje
03.12.2010-05.12.2010
Beč, Austrija