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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-36032

Pinschewer, D D; Flatz, L; Steinborn, R; Horvath, E; Fernandez, M; Lutz, H; Suter, M; Bergthaler, A (2010). Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes. International Immunology, 22(9):749-756.

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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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Department of Farm Animals > Clinical Laboratory
04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology
05 Vetsuisse Faculty > Institute of Virology
DDC:570 Life sciences; biology
610 Medicine & health
630 Agriculture
Date:2010
Deposited On:11 Nov 2010 14:23
Last Modified:14 Dec 2013 17:18
Publisher:Oxford University Press
ISSN:0953-8178
Publisher DOI:10.1093/intimm/dxq061
PubMed ID:20584765

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