J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells

Taylor, Patricia R.; Koski, Gary K.; Paustian, Christopher; Bailey, Erin; Cohen, Peter A.; Moore, Francisco B.‐G.; Zimmerman, Daniel H.; Rosenthal, Ken S.

doi:10.1016/j.vaccine.2010.06.043

Cited by 21 publications

(47 citation statements)

References 34 publications

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“…As expected based on similar studies for other LEAPS immunogens, CEL-2000 caused an increase in IL-12p70 [45]. Unlike previously examined LEAPS immunogens, CEL-2000 induced an increase in IL-10 levels with concurrent reduction in levels of TNF-α, IL-17, IL-6, MCP-1 and IL-12p40.…”

Section: Effect Of Cel-2000 Vaccine Therapy On Serum Cytokinessupporting

confidence: 83%

“…The cytokine response to CEL-2000 was similar to that of naïve C57BL/6 mice immunized with two other J-I/TCBL immunogens, JgD or JH, for which there was also an increase in IL-12p70 with no increase in TNF-α, IL-1 or IL-10 [45]. The induction of an IL-10 response by CEL-2000 may be unique to this immunogen or due to the immune response to a self antigen represented by the epitope within CEL-2000.…”

Section: Discussionmentioning

confidence: 60%

“…Administration of the CEL-2000 in an oil-in-water emulsion with either the MAS-1 or the Seppic ISA-51 adjuvant gave similar positive results. ISA-51 has been used with other J-LEAPS vaccines [29][30][31][32]38] but is not necessary to initiate immunomodulatory cytokine production by J-LEAPS immunogens [45]. The depot effect of the emulsion providing slow release and extended CEL-2000 action may be more important to the efficacy of CEL-2000 than possible adjuvant effects of these formulations.…”

Section: Discussionmentioning

confidence: 99%

“…A similar approach was used to monitor the immune response to other LEAPS vaccines [45]. The results are shown in Table 1.…”

Section: Effect Of Cel-2000 Vaccine Therapy On Serum Cytokinesmentioning

confidence: 99%

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CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

Zimmerman

Taylor

Bendele³

et al. 2010

International Immunopharmacology

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Section: Effect Of Cel-2000 Vaccine Therapy On Serum Cytokinessupporting

confidence: 83%

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

“…A similar approach was used to monitor the immune response to other LEAPS vaccines [45]. The results are shown in Table 1.…”

Section: Effect Of Cel-2000 Vaccine Therapy On Serum Cytokinesmentioning

confidence: 99%

See 2 more Smart Citations

CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

Zimmerman

Taylor

Bendele³

et al. 2010

International Immunopharmacology

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“…DCs recognize distinct components of HSV (22,48,50). When pulsed with a gD peptide ex vivo, DCs confer protective immunity upon adoptive transfer (58). To assess the ␥ 1 34.5 null mutant, immature CD11c ϩ DCs derived from bone marrow were mock infected or infected with R3616 ex vivo for 12 h. After washing, the DCs were transferred into naïve mice and challenged with wild-type virus (1 ϫ 10 7 PFU).…”

Section: Immunizationmentioning

confidence: 99%

Activation of NF-κB in CD8 ⁺ Dendritic Cells Ex Vivo by the γ ₁ 34.5 Null Mutant Correlates with Immunity against Herpes Simplex Virus 1

Jin

Yan

et al. 2012

J Virol

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The ␥ 1 34.5 protein of herpes simplex viruses (HSV) is essential for virulence. Accordingly, an HSV mutant lacking ␥ 1 34.5 is attenuated in vivo. Despite its vaccine potential, the mechanism by which the ␥ 1 34.5 null mutant triggers protective immunity is unknown. In this report we show that vaccination with the ␥ 1 34.5 null mutant protects against lethal challenge from wild-type virus via IB kinase in dendritic cells (DCs), which sense virus-associated molecular patterns. Unlike mock-treated DCs, DCs primed with the ␥ 1 34.5 null mutant ex vivo mediate resistance to wild-type HSV after adoptive transfer into naïve mice. Furthermore, the ␥ 1 34.5 null mutant activates IB kinase, which facilitates p65/RelA phosphorylation and nuclear translocation, resulting in DC maturation. While unable to produce infectious virus in DCs, this mutant virus expresses early and late genes. In its abortive infection, the ␥ 1 34.5 null mutant induces protective immunity more effectively in CD8 ؉ DCs than in CD8 ؊ DCs. This is mirrored by a higher level of interleukin-6 (IL-6) and IL-12 secretion by CD8 ؉ DCs than CD8 ؊ DCs. Remarkably, inhibition of p65/RelA phosphorylation or nuclear translocation in CD8 ؉ DCs disrupts protective immunity. These results suggest that engagement of the ␥ 1 34.5 null mutant with CD8 ؉ DCs elicits innate immunity to activate NF-B, which translates into protective immunity. Herpes simplex viruses (HSVs) are human pathogens responsible for a spectrum of diseases, including ocular lesions, genital herpes, and encephalitis (11). HSV infection is also a risk factor in HIV acquisition and transmission. Following infection, HSV initiates a lytic cycle in the mucosal tissues, where viral gene transcription, replication, assembly, and egress ensue. This is followed by a latency in sensory ganglia, where reactivation occurs intermittently, resulting in recurrent infections (11). In this process, HSV interacts with host cells, including dendritic cells (DCs), which capture, process, and present viral antigens. Upon maturation, DCs express high levels of costimulatory molecules. Additionally, DCs release inflammatory cytokines to induce T cell responses that restrict viral infection (1, 54, 68).DCs detect HSV through multiple pathways (22,48,50). For example, plasmacytoid DCs detect HSV through Toll-like receptor 9 (TLR9), whereas conventional DCs sense virus via TLRdependent and -independent pathways (22,32,48). It is thought that HSV proteins or RNA intermediates trigger conventional DCs (22,48). Notably, a complex consisting of HSV glycoproteins B, D, H, and L stimulates DC maturation (50). On the other hand, HSV blocks DC activities (3,26,28,52). In immature DCs, HSV type 1 (HSV-1) downregulates cell surface molecules and cytokines, impairing T cell activation (10, 26, 38, 44, 52). HSV-1 also induces apoptosis of DCs, whereas HSV-2 exerts this activity more rapidly (5, 26, 44). Further, HSV-1 perturbs mature DCs (28, 45), where it induces degradation of CD83 (28, 29). Moreover, HSV-1 reduces levels of che...

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Recombinant Vaccines: Development, Production, and Application

Grand¹,

White²,

Siegel³

et al. 2012

Pharmaceutical Biotechnology

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J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells

Cited by 21 publications

References 34 publications

CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

Activation of NF-κB in CD8 ⁺ Dendritic Cells Ex Vivo by the γ ₁ 34.5 Null Mutant Correlates with Immunity against Herpes Simplex Virus 1

Recombinant Vaccines: Development, Production, and Application

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J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells

Cited by 21 publications

References 34 publications

CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

Activation of NF-κB in CD8 + Dendritic Cells Ex Vivo by the γ 1 34.5 Null Mutant Correlates with Immunity against Herpes Simplex Virus 1

Recombinant Vaccines: Development, Production, and Application

Contact Info

Product

Resources

About

Activation of NF-κB in CD8 ⁺ Dendritic Cells Ex Vivo by the γ ₁ 34.5 Null Mutant Correlates with Immunity against Herpes Simplex Virus 1