Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity

Flatz, Lukas; Hegazy, Ahmed N.; Bergthaler, Andreas; Verschoor, Admar; Claus, Christina; Fernandez, Marylise; Gattinoni, Luca; Johnson, Susan; Kreppel, Florian; Kochanek, Stefan; Broek, Maries van den; Radbruch, Andreas; Lévy, Frédéric; Lambert, Paul-Henri; Siegrist, Claire-Anne; Restifo, Nicholas P.; Löhning, Max; Ochsenbein, Adrian F.; Nabel, Gary J. and Pinschewer, Daniel D. (2010). Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity. Nature medicine, 16(3), pp. 339-345. New York, N.Y.: Nature Publishing Group 10.1038/nm.2104

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Lymphocytic choriomeningitis virus (LCMV) exhibits natural tropism for dendritic cells and represents the prototypic infection that elicits protective CD8(+) T cell (cytotoxic T lymphocyte (CTL)) immunity. Here we have harnessed the immunobiology of this arenavirus for vaccine delivery. By using producer cells constitutively synthesizing the viral glycoprotein (GP), it was possible to replace the gene encoding LCMV GP with vaccine antigens to create replication-defective vaccine vectors. These rLCMV vaccines elicited CTL responses that were equivalent to or greater than those elicited by recombinant adenovirus 5 or recombinant vaccinia virus in their magnitude and cytokine profiles, and they exhibited more effective protection in several models. In contrast to recombinant adenovirus 5, rLCMV failed to elicit vector-specific antibody immunity, which facilitated re-administration of the same vector for booster vaccination. In addition, rLCMV elicited T helper type 1 CD4+ T cell responses and protective neutralizing antibodies to vaccine antigens. These features, together with low seroprevalence in humans, suggest that rLCMV may show utility as a vaccine platform against infectious diseases and cancer.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Ochsenbein, Adrian

ISSN:

1078-8956

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:09

Last Modified:

27 Jun 2014 11:14

Publisher DOI:

10.1038/nm.2104

PubMed ID:

20139992

Web of Science ID:

000275289500042

URI:

https://boris.unibe.ch/id/eprint/1081 (FactScience: 201828)

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