Scientific Article
previous document  unige:11517  next document
add to browser collection
Title

Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes

Authors
Flatz, Lukas
Steinborn, R.
Horvath, Edith
Lutz, H.
Suter, M.
Published in International Immunology. 2010, vol. 22, no. 9, p. 749-756
Abstract Arenaviruses such as Lassa virus (LASV) cause significant morbidity and mortality in endemic areas. Using a glycoprotein (GP) exchange strategy, we have recently developed live-attenuated arenavirus vaccine prototypes (rLCMV/VSVG) based on lymphocytic choriomeningitis virus (LCMV), a close relative of LASV. rLCMV/VSVG induced long-term CD8(+) T cell immunity against wild-type virus challenge and exhibited a stably attenuated phenotype in vivo. Here we elucidated the innate and adaptive immune requirements for the control of rLCMV/VSVG. Infection of RAG(-/-) mice resulted in persisting viral RNA in blood but not in overt viremia. The latter was only found in mice lacking both RAG and IFN type I receptor. Conversely, absence of IFN type II signaling or NK cells on an RAG-deficient background had only minor effects on vaccine virus load or none at all. rLCMV/VSVG infection of wild-type mice induced less type I IFN than did wild-type LCMV, and type I as well as type II IFNs were dispensable for the induction of virus-specific memory CD8 T cells and virus-neutralizing antibodies by rLCMV/VSVG. In conclusion, the adaptive immune systems are essential for elimination of rLCMV/VSVG, and type I but not type II IFN plays a major contributive role in lowering rLCMV/VSVG loads in vivo, attesting to the attenuation profile of the vaccine. Nevertheless, IFNs are not required for the induction of potent vaccine responses. These results provide a better understanding of the immunobiology of rLCMV/VSVG and will contribute to the further development of GP exchange vaccines for combating arenaviral hemorrhagic fevers.
Identifiers
PMID: 20584765
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://intimm.oxfordjournals.org/cgi/reprint/dxq061v1.pdf
Citation
(ISO format)
PINSCHEWER, Daniel et al. Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes. In: International Immunology, 2010, vol. 22, n° 9, p. 749-756. https://archive-ouverte.unige.ch/unige:11517

185 hits

0 download

Update

Deposited on : 2010-08-27

Export document
Format :
Citation style :