BAC-VAC, a novel generation of (DNA) vaccines: A bacterial artificial chromosome (BAC) containing a replication-competent, packaging-defective virus genome induces protective immunity against herpes simplex virus 1

Suter, Mark; Lew, Andrew M.; Grob, Philipp; Adema, Gosse J.; Ackermann, Mathias; Shortman, Ken; Fraefel, Cornel

doi:10.1073/pnas.96.22.12697

Cited by 68 publications

(56 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SGVs differ from the recently described BAC-VAC vector that delivers the entire HSV-1 genome as a DNA vaccine. 19,20 Much like a live virus vaccine, BAC-VAC immunization would be expected to initiate an infectious cycle where viral proteins can regulate the viral promoters. An SGV, however, does not contain the entire complement of viral genes, and is, therefore, non-infectious but the promoters are still responsive to host cell transcription factors.…”

Section: Discussionmentioning

confidence: 99%

Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments

Braun¹,

Dong²,

Jerome³

et al. 2008

Human Vaccines

View full text Add to dashboard Cite

A novel DNA vaccine was generated using genomic fragments of a pathogen as the source of both the antigen coding and regulatory regions. The constructs, termed subgenomic vaccines (SGVs), incorporated genomic DNA sequences up to 45 kbp that encompass 15-20 different genes. The SGVs were developed to generate vaccines capable of expressing multiple genes from a single construct, which could be of great benefit for commercialization. The unique feature of the SGVs is that genes are expressed from their native promoters rather than heterologous promoters typical of DNA vaccines. SGVs composed of genomic fragments from the DS-DNA virus Herpes Simplex Virus Type 2 (HSV-2) induced HSV-2 specific immune responses following particle-mediated epidermal delivery (PMED) in mice and these responses protected animals from lethal infectious challenge. A second generation SGV (SGV-H2), intended as an HSV-2 therapeutic vaccine, was generated that had five HSV-2 genes and was capable of generating multi-antigenic responses in naïve mice, and enhancing responses in infected animals. When compared with standard single plasmid vaccines, immunization with the SGV-H2 was found to be at least as effective as single plasmids or plasmid mixtures. The activity of the SGV-H2 could be greatly enhanced by co-delivering plasmids expressing E. coli heat labile toxin (LT) or cholera toxin CT as adjuvants as has been found previously for standard single-gene DNA vaccines.

show abstract

Section: Discussionmentioning

confidence: 99%

Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments

Braun¹,

Dong²,

Jerome³

et al. 2008

Human Vaccines

View full text Add to dashboard Cite

show abstract

“…Resiquimod (R848) was a gift of G. Lipford (Coley Pharmaceutical, Langenfeld, Germany). HSV-1 (F strain) was originally obtained from B. Roizman (University of Chicago, Chicago), propagated on Vero cells, and isolated as described (20). In short, to harvest viral particles, the infected cells were scraped into medium, the suspension was frozen and thawed three times and sonicated, and the cell debris was removed by centrifugation.…”

Section: Methodsmentioning

confidence: 99%

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

Hochrein

Schlatter

O’Keeffe

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

398

332

View full text Add to dashboard Cite

Type I IFN production in response to the DNA virus herpes simplex virus type-1 (HSV-1) is essential in controlling viral replication. We investigated whether plasmacytoid dendritic cells (pDC) were the major tissue source of IFN-␣, and whether the production of IFN-␣ in response to HSV-1 depended on Toll-like receptor 9 (TLR9). Total spleen cells or bone marrow (BM) cells, or fractions thereof, including highly purified pDC, from WT, TLR9, and MyD88 knockout mice were stimulated with known ligands for TLR9 or active HSV-1. pDC freshly isolated from both spleen and BM were the major source of IFN-␣ in response to oligodeoxynucleotides containing CpG motifs, but in response to HSV-1 the majority of IFN-␣ was produced by other cell types. Moreover, IFN-␣ production by non-pDC was independent of TLR9. The tissue source determined whether pDC responded to HSV-1 in a strictly TLR9-dependent fashion. Freshly isolated BM pDC or pDC derived from culture of BM precursors with FMS-like tyrosine kinase-3 ligand, produced IFN-␣ in the absence of functional TLR9, whereas spleen pDC did not. Heat treatment of HSV-1 abolished maturation and IFN-␣ production from all TLR9-deficient DC but not WT DC. Thus pDC and non-pDC produce IFN-␣ in response to HSV-1 via both TLR9-independent and -dependent pathways.

show abstract

“…The HSV-1 F strain was originally obtained from B. Roizmann (University of Chicago, USA) and propagated on Vero cells. For all experiments, virus particles were used after purification by ultracentrifugation on a sucrose density gradient, and the virus titer (PFU) was determined as described [36,37].…”

Section: Methodsmentioning

confidence: 99%

The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

Vollstedt¹,

O’Keeffe²,

Ryf³

et al. 2006

Eur J Immunol

Self Cite

View full text Add to dashboard Cite

The cooperation between IFN-a/b and FL, the ligand of Fms-like tyrosine kinase 3 (Flt3), plays an important role in the defense against herpes simplex virus type 1 (HSV-1) in neonates. Treatment of neonatal mice with recombinant IFN-a has a shortterm, FL-independent and a long-term, FL-dependent protective effect against HSV-1. In mice lacking FL, neonatal resistance against HSV-1 is very low and DC numbers in the spleen are reduced. The treatment of these mice with rIFN-a at day 6 resulted in an increased resistance against infection with HSV-1 at day 7. In C57BL/6 mice, treatment with rIFN-a at birth induced both FL and plasmacytoid DC (pDC), resulting in enhanced resistance against HSV-1 at day 7. In contrast, in mice lacking FL, IFN-a treatment at birth did not influence the splenic cell composition and had no effect on viral protection. The transfer of pDC to mice lacking FL enhanced viral resistance. Therefore, the induction and function of pDC, normally controlled by IFN-a/b and FL, are decisive for viral resistance in neonatal mice.

show abstract

BAC-VAC, a novel generation of (DNA) vaccines: A bacterial artificial chromosome (BAC) containing a replication-competent, packaging-defective virus genome induces protective immunity against herpes simplex virus 1

Cited by 68 publications

References 50 publications

Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments

Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

Contact Info

Product

Resources

About