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.
| Language | English (US) |
|---|---|
| Pages | 339-345 |
| Number of pages | 7 |
| Journal | Nature Medicine |
| Volume | 16 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity
AU - Flatz, Lukas
AU - Hegazy, Ahmed N.
AU - Bergthaler, Andreas
AU - Verschoor, Admar
AU - Claus, Christina
AU - Fernandez, Marylise
AU - Gattinoni, Luca
AU - Johnson, Susan
AU - Kreppel, Florian
AU - Kochanek, Stefan
AU - Broek, Maries Van Den
AU - Radbruch, Andreas
AU - Lévy, Frédéric
AU - Lambert, Paul Henri
AU - Siegrist, Claire Anne
AU - Restifo, Nicholas P.
AU - Löhning, Max
AU - Ochsenbein, Adrian F.
AU - Nabel, Gary J.
AU - Pinschewer, Daniel D.
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
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U2 - 10.1038/nm.2104
DO - 10.1038/nm.2104
M3 - Article
VL - 16
SP - 339
EP - 345
JO - Nature Medicine
T2 - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 3
ER -