Cutting Edge: A Potent Adjuvant Effect of Ligand to Receptor Activator of NF-κB Gene for Inducing Antigen-Specific CD8+ T Cell Response by DNA and Viral Vector Vaccination

Miyahira, Yasushi; Akiba, Hisaya; Katae, Masaharu; Kubota, Kaori; Kobayashi, Seiki; Takeuchi, Tsutomu; Garcı́a-Sastre, Adolfo; Fukuchi, Yoshinosuke; Okumura, Ko; Yagita, Hideo; Aoki, Takashi

doi:10.4049/jimmunol.171.12.6344

Cited by 25 publications

(18 citation statements)

References 23 publications

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“…In all of these cases, the antigen used in the DNA vaccine was cell associated, i.e., located either in the cytoplasm, like ␤-galactosidase (13,60), or on the cell membrane, like HIV-1 gp160 (39) or respiratory syncytial virus envelope (31). In contrast, the present report and two previous reports failed to find any adjuvant effects with pMemCD40L-like plasmids when secreted antigens were studied (e.g., TSSA from Treponema cruzi [61] or gp120 [88]). Antigen localization has been previously identified as an important variable for DNA vaccination (12,62,69,75,89) and has implications for the selection of adjuvanting molecules.…”

Section: Discussioncontrasting

confidence: 54%

“…3B). The addition of a plasmid for membrane CD40L (pMemCD40L) to the pScGag vaccine had no effect on these elicited responses, in contrast to several reports (13,31,39,57,60,80,96) but consistent with two recent reports on DNA vaccination (61,88). Remarkably, the plasmid for 4-trimer soluble CD40L (pSP-D-CD40L) significantly augmented the response to the pScGag DNA vaccine (Fig.…”

Section: Construction Of Expression Plasmids For 1- 2- and 4-trimercontrasting

confidence: 49%

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Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Stone¹,

Barzee²,

Snarsky³

et al. 2006

J Virol

115

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For use in humans, human immunodeficiency virus (HIV) DNA vaccines may need to include immunostimulatory adjuvant molecules. CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily (TNFSF), is one candidate adjuvant, but it has been difficult to use because it is normally expressed as a trimeric membrane molecule. Soluble trimeric forms of CD40L have been produced, but in vitro data indicate that multimeric, many-trimer forms of soluble CD40L are more active. This multimerization requirement was evaluated in mice using plasmids that encoded either 1-trimer, 2-trimer, or 4-trimer soluble forms of CD40L. Fusion with the body of Acrp30 was used to produce the 2-trimer form, and fusion with the body of surfactant protein D was used to produce the 4-trimer form. Using plasmids for secreted HIV-1 antigens Gag and Env, soluble CD40L was active as an adjuvant in direct proportion to the valence of the trimers (1 < 2 < 4). These CD40L-augmented DNA vaccines elicited strong CD8 ؉ T-cell responses but did not elicit significant CD4 ؉ T-cell or antibody responses. To test the applicability of the multimeric fusion protein approach to other TNFSFs, a 4-trimer construct for the ligand of glucocorticoid-induced TNF family-related receptor (GITR) was also prepared. Multimeric soluble GITR ligand (GITRL) augmented the CD8 ؉ T-cell, CD4 ؉ T-cell, and antibody responses to DNA vaccination. In summary, multimeric CD40L and GITRL are new adjuvants for DNA vaccines. Plasmids for expressing multimeric TNFSF fusion proteins permit the rapid testing of TNFSF molecules in vivo.

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Section: Discussioncontrasting

confidence: 54%

Section: Construction Of Expression Plasmids For 1- 2- and 4-trimercontrasting

confidence: 49%

Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Stone¹,

Barzee²,

Snarsky³

et al. 2006

J Virol

115

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“…We designated the "surface protein" TSSA, since its amino acid sequence was highly homologous to the T. cruzi trans-sialidase superfamily protein. Although we have not determined yet whether the TSSA actually has neuraminidase and trans-sialidase activities, we demonstrated that the DNA encoding TSSA was highly immunogenic, conferring protective immunity in C57BL/6 mice against T. cruzi infection (19,27,28,29).…”

Section: Animals and Parasite Female C57bl/6 (H-2mentioning

confidence: 99%

“…An H-2K b -restricted CD8 ϩ -T-cell epitope peptide, ANYNFTLV, derived from TSSA (19,27,28,29) (Fig. 1A) was synthesized and used for immunological assays.…”

Section: Animals and Parasite Female C57bl/6 (H-2mentioning

confidence: 99%

Immune Responses against a Single CD8⁺-T-Cell Epitope Induced by Virus Vector Vaccination Can Successfully ControlTrypanosoma cruziInfection

Miyahira¹,

Takashima

Kobayashi

et al. 2005

Infect Immun

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In order to develop CD8؉ -T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8؉ -T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8 ؉ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8؉ -T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8؉ -T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NFB (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8 ؉

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“…Adjuvant effects were consistently observed if the antigen was located in the cytoplasm (6,10) or on the cell membrane (7,8). However, adjuvant effects were not observed if the antigen was secreted (28)(29)(30). This becomes a limitation for HIV vaccines expressing virus-like particles (VLPs) and secreted forms of Env (important for high levels of Ab production).…”

mentioning

confidence: 99%

CD40L-Adjuvanted DNA/Modified Vaccinia Virus Ankara Simian Immunodeficiency Virus SIV239 Vaccine Enhances SIV-Specific Humoral and Cellular Immunity and Improves Protection against a Heterologous SIVE660 Mucosal Challenge

Kwa

Lai

Gangadhara

et al. 2014

J Virol

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It remains a challenge to develop a successful human immunodeficiency virus (HIV) vaccine that is capable of preventing infection. Here, we utilized the benefits of CD40L, a costimulatory molecule that can stimulate both dendritic cells (DCs) and B cells, as an adjuvant for our simian immunodeficiency virus (SIV) DNA vaccine in rhesus macaques. We coexpressed the CD40L with our DNA/SIV vaccine such that the CD40L is anchored on the membrane of SIV virus-like particle (VLP). These CD40L containing SIV VLPs showed enhanced activation of DCs in vitro. We then tested the potential of DNA/SIV-CD40L vaccine to adjuvant the DNA prime of a DNA/modified vaccinia virus Ankara (MVA) vaccine in rhesus macaques. Our results demonstrated that the CD40L adjuvant enhanced the functional quality of anti-Env antibody response and breadth of anti-SIV CD8 and CD4 T cell responses, significantly delayed the acquisition of heterologous mucosal SIV infection, and improved viral control. Notably, the CD40L adjuvant enhanced the control of viral replication in the gut at the site of challenge that was associated with lower mucosal CD8 immune activation, one of the strong predictors of disease progression. Collectively, our results highlight the benefits of CD40L adjuvant for enhancing antiviral humoral and cellular immunity, leading to enhanced protection against a pathogenic SIV. A single adjuvant that enhances both humoral and cellular immunity is rare and thus underlines the importance and practicality of CD40L as an adjuvant for vaccines against infectious diseases, including HIV-1. IMPORTANCEDespite many advances in the field of AIDS research, an effective AIDS vaccine that can prevent infection remains elusive. CD40L is a key stimulator of dendritic cells and B cells and can therefore enhance T cell and antibody responses, but its overly potent nature can lead to adverse effects unless used in small doses. In order to modulate local expression of CD40L at relatively lower levels, we expressed CD40L in a membrane-bound form, along with SIV antigens, in a nucleic acid (DNA) vector. We tested the immunogenicity and efficacy of the CD40L-adjuvanted vaccine in macaques using a heterologous mucosal SIV infection. The CD40L-adjuvanted vaccine enhanced the functional quality of anti-Env antibody response and breadth of anti-SIV T cell responses and improved protection. These results demonstrate that VLP-membrane-bound CD40L serves as a novel adjuvant for an HIV vaccine. N ovel vaccine approaches that elicit strong humoral and cellular immunity with high functional quality will aid HIV vaccine development. Here, we utilized the benefits of CD40L, a costimulatory molecule belonging to the tumor necrosis factor superfamily (TNFSF), that can stimulate both dendritic cells (DCs) and B cells for enhancing T cell and antibody (Ab) responses (1). CD40L activates DCs and enhances the priming of the cytotoxic CD8 T cell response (2-4). CD40L also enhances the survival and differentiation of activated B cells, leading to increased germinal c...

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Cutting Edge: A Potent Adjuvant Effect of Ligand to Receptor Activator of NF-κB Gene for Inducing Antigen-Specific CD8+ T Cell Response by DNA and Viral Vector Vaccination

Cited by 25 publications

References 23 publications

Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Immune Responses against a Single CD8⁺-T-Cell Epitope Induced by Virus Vector Vaccination Can Successfully ControlTrypanosoma cruziInfection

CD40L-Adjuvanted DNA/Modified Vaccinia Virus Ankara Simian Immunodeficiency Virus SIV239 Vaccine Enhances SIV-Specific Humoral and Cellular Immunity and Improves Protection against a Heterologous SIVE660 Mucosal Challenge

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Cutting Edge: A Potent Adjuvant Effect of Ligand to Receptor Activator of NF-κB Gene for Inducing Antigen-Specific CD8+ T Cell Response by DNA and Viral Vector Vaccination

Cited by 25 publications

References 23 publications

Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Immune Responses against a Single CD8+-T-Cell Epitope Induced by Virus Vector Vaccination Can Successfully ControlTrypanosoma cruziInfection

CD40L-Adjuvanted DNA/Modified Vaccinia Virus Ankara Simian Immunodeficiency Virus SIV239 Vaccine Enhances SIV-Specific Humoral and Cellular Immunity and Improves Protection against a Heterologous SIVE660 Mucosal Challenge

Contact Info

Product

Resources

About

Immune Responses against a Single CD8⁺-T-Cell Epitope Induced by Virus Vector Vaccination Can Successfully ControlTrypanosoma cruziInfection