Current Status of Immunological Adjuvants

Warren, H. Shaw; Vogel, Frederick R.; Chedid, L

doi:10.1146/annurev.iy.04.040186.002101

Cited by 266 publications

(112 citation statements)

References 47 publications

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“…However, the TLR2 agonist Pam2Cys acts as a self-adjuvant when directly conjugated to peptides. It then binds specifically to TLR2 on APCs and directs peptide uptake by the same cells (53)(54)(55). After uptake of these in PBMCs, presumably by TLR2-expressing NK cells, monocytes, and myeloid DCs, Pam2Cys conjugation to the two gD2 peptides markedly enhanced CD4 T lymphocyte IFN-g responses, as shown by IFN-g ELISPOT.…”

Section: Discussionmentioning

confidence: 98%

Herpes Simplex Virus Antigens Directly Activate NK Cells via TLR2, Thus Facilitating Their Presentation to CD4 T Lymphocytes

Kim

Osborne

Zeng

et al. 2012

The Journal of Immunology

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NK cells infiltrate human herpetic lesions, but their role has been underexplored. HSV can stimulate innate immune responses via surface TLR2, which is expressed on monocyte-derived dendritic cells (DCs) and NK cells. In this study, UV-inactivated HSV1/2 and immunodominant HSV2 glycoprotein D peptides conjugated to the TLR2 agonist dipalmitoyl-S-glyceryl cysteine stimulated CD4 T lymphocyte IFN-γ responses within PBMCs or in coculture with monocyte-derived DCs. NK cells contributed markedly to the PBMC responses. Furthermore, NK cells alone were activated directly by both Ags, also upregulating HLA-DR and HLA-DQ and then they activated autologous CD4 T lymphocytes. Using Transwells, Ag-stimulated NK cells and CD4 T lymphocytes were shown to interact through both cell-to-cell contact and cytokines, differing in relative importance in different donors. A distinct immunological synapse between Ag-stimulated NK cells and CD4 T lymphocytes was observed, indicating the significance of their cell-to-cell contact. A large proportion (57%) of NK cells was also in contact with CD4 T lymphocytes in the dermal infiltrate of human recurrent herpetic lesions. Thus, NK cells stimulated by TLR2-activating HSV Ags can present Ag alone or augment the role of DCs in vitro and perhaps in herpetic lesions or draining lymph nodes. In addition to DCs, NK cells should be considered as targets for adjuvants during HSV vaccine development.

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Section: Discussionmentioning

confidence: 98%

Herpes Simplex Virus Antigens Directly Activate NK Cells via TLR2, Thus Facilitating Their Presentation to CD4 T Lymphocytes

Kim

Osborne

Zeng

et al. 2012

The Journal of Immunology

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“…The severe side effects caused primarily by the paraffin oil contained in these adjuvants precluded a detailed analysis of their mode of action (35) and their use in humans. There is accumulating evidence that CpG-DNA acts as a potent vaccine adjuvant for promoting Th-1-like immune responses (16 -19, 36).…”

Section: Discussionmentioning

confidence: 99%

CpG-DNA Activates In Vivo T Cell Epitope Presenting Dendritic Cells to Trigger Protective Antiviral Cytotoxic T Cell Responses

Vabulas

Pircher

Lipford

et al. 2000

The Journal of Immunology

119

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MHC class I-restricted T cell epitopes lack immunogenicity unless aided by IFA or CFA. In an attempt to circumvent the known inflammatory side effects of IFA and CFA, we analyzed the ability of immunostimulatory CpG-DNA to act as an adjuvant for MHC class I-restricted peptide epitopes. Using the immunodominant CD8 T cell epitopes, SIINFEKL from OVA or KAVYNFATM (gp33) from lymphocytic choriomeningitis virus glycoprotein, we observed that CpG-DNA conveyed immunogenicity to these epitopes leading to primary induction of peptide-specific CTL. Furthermore, vaccination with the lymphocytic choriomeningitis virus gp33 peptide triggered not only CTL but also protective antiviral defense. We also showed that MHC class I-restricted peptides are constitutively presented by immature dendritic cells (DC) within the draining lymph nodes but failed to induce CTL responses. The use of CpG-DNA as an adjuvant, however, initiated peptide presenting immature DC progression to professional licensed APC. Activated DC induced cytolytic CD8 T cells in wild-type mice and also mice deficient of Th cells or CD40 ligand. CpG-DNA thus incites CTL responses toward MHC class I-restricted T cell epitopes in a Th cell-independent manner. Overall, these results provide new insights into CpG-DNA-mediated adjuvanticity and may influence future vaccination strategies for infectious and perhaps tumor diseases.

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“…Clarke et al (24) produced a highly immunogenic preparation by presenting multiple copies of a peptide antigen using the hepatitis B core antigen. Lipid matrices, such as liposomes (10,11) and immunostimulating complex ISCOM (9), also allow noncovalent organization of multimeric presentation of antigens on their surface. ISCOM is a stable lipid matrix that contains cholesterol and Quil A, a plant extract that also serves as an adjuvant.…”

Section: Discussionmentioning

confidence: 99%

Macromolecular assemblage in the design of a synthetic AIDS vaccine.

Defoort

Nardelli

Huang

et al. 1992

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

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We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the antigens many-fold in liposomal or micellar form. A peptide antigen derived from the third variable domain of glycoprotein gpl20 of human immunodeficiency virus type 1 (HIV-1

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Current Status of Immunological Adjuvants

Cited by 266 publications

References 47 publications

Herpes Simplex Virus Antigens Directly Activate NK Cells via TLR2, Thus Facilitating Their Presentation to CD4 T Lymphocytes

Herpes Simplex Virus Antigens Directly Activate NK Cells via TLR2, Thus Facilitating Their Presentation to CD4 T Lymphocytes

CpG-DNA Activates In Vivo T Cell Epitope Presenting Dendritic Cells to Trigger Protective Antiviral Cytotoxic T Cell Responses

Macromolecular assemblage in the design of a synthetic AIDS vaccine.

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