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

Lukas Flatz, Ahmed N. Hegazy, Andreas Bergthaler, Admar Verschoor, Christina Claus, Marylise Fernandez, Luca Gattinoni, Susan Johnson, Florian Kreppel, Stefan Kochanek, Maries Van Den Broek, Andreas Radbruch, Frédéric Lévy, Paul Henri Lambert, Claire Anne Siegrist, Nicholas P. Restifo, Max Löhning, Adrian F. Ochsenbein, Gary J. Nabel, Daniel D. Pinschewer

Research output: Contribution to journalArticle

Abstract

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+ 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.

LanguageEnglish (US)
Pages339-345
Number of pages7
JournalNature Medicine
Volume16
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

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Lymphocytic choriomeningitis virus
Defective Viruses
Virus Activation
T-cells
Viruses
Immunity
Vaccines
T-Lymphocytes
Cytotoxic T-Lymphocytes
Adenoviridae
Glycoproteins
Arenavirus
Antigens
Th1 Cells
Gene encoding
Tropism
Vaccinia virus
Seroepidemiologic Studies
Neutralizing Antibodies
Dendritic Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Flatz, L., Hegazy, A. N., Bergthaler, A., Verschoor, A., Claus, C., Fernandez, M., ... Pinschewer, D. D. (2010). Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity. Nature Medicine, 16(3), 339-345. https://doi.org/10.1038/nm.2104

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.; Pinschewer, Daniel D.

In: Nature Medicine, Vol. 16, No. 3, 03.2010, p. 339-345.

Research output: Contribution to journalArticle

Flatz, L, Hegazy, AN, Bergthaler, A, Verschoor, A, Claus, C, Fernandez, M, Gattinoni, L, Johnson, S, Kreppel, F, Kochanek, S, Broek, MVD, Radbruch, A, Lévy, F, Lambert, PH, Siegrist, CA, Restifo, NP, Löhning, M, Ochsenbein, AF, Nabel, GJ & Pinschewer, DD 2010, 'Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity' Nature Medicine, vol. 16, no. 3, pp. 339-345. https://doi.org/10.1038/nm.2104
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. ; Pinschewer, Daniel D. / Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity. In: Nature Medicine. 2010 ; Vol. 16, No. 3. pp. 339-345.
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