Role of CD80 and CD86 in host immune responses to the recombinant hemagglutinin domain of Porphyromonas gingivalis gingipain and in the adjuvanticity of cholera toxin B and monophosphoryl lipid A

Zhang, Ping; Lewis, Janina P.; Michalek, Suzanne M.; Katz, Jannet

doi:10.1016/j.vaccine.2007.05.066

Cited by 16 publications

(18 citation statements)

References 47 publications

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“…CD80 and CD86 share ∼27% external domain homology and activate the bidirectional signaling by engaging either the immunostimulatory CD28 or the inhibitory CTLA-4 receptors on T cells (18,84). Consistent with other studies, mice lacking CD86 produced normal Ab titers, whereas double CD80/CD86 mutation completely abolished this response and severely reduced a Th-1 bias of immunity (85,86). This suggests that NE activates either CD80 or CD86 signaling, and CD80 activation alone is sufficient for the B cell-dependent IgG response but not for Th-1-type cell immunity.…”

Section: Discussionsupporting

confidence: 82%

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Bielinska

Makidon

Janczak

et al. 2014

The Journal of Immunology

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Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1– and Th-17–balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell–mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses.

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Section: Discussionsupporting

confidence: 82%

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Bielinska

Makidon

Janczak

et al. 2014

The Journal of Immunology

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“…This response is associated with the rapid migration of Ag loaded and activated DCs to the draining lymph nodes. The elevated expression of CD40/86 in DCs is known to be critical for the Ag-specific activation of Th cells (59) and the optimal activation of APCs favors the local induction of Th cells expressing TCRs with the highest affinity to antigenic peptides (60). An MPL-based adjuvant has been found to specifically activate local follicular Th cells that are thought to be directly associated with the generation of B cell memory (61,62).…”

Section: How Does As04 Enhance Ab Response Compared With Aluminum Hydmentioning

confidence: 99%

AS04, an Aluminum Salt- and TLR4 Agonist-Based Adjuvant System, Induces a Transient Localized Innate Immune Response Leading to Enhanced Adaptive Immunity

Didierlaurent

Morel

Lockman

et al. 2009

The Journal of Immunology

624

471

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Adjuvant System 04 (AS04) combines the TLR4 agonist MPL (3-O-desacyl-4′-monophosphoryl lipid A) and aluminum salt. It is a new generation TLR-based adjuvant licensed for use in human vaccines. One of these vaccines, the human papillomavirus (HPV) vaccine Cervarix, is used in this study to elucidate the mechanism of action of AS04 in human cells and in mice. The adjuvant activity of AS04 was found to be strictly dependent on AS04 and the HPV Ags being injected at the same i.m. site within 24 h of each other. During this period, AS04 transiently induced local NF-κB activity and cytokine production. This led to an increased number of activated Ag-loaded dendritic cells and monocytes in the lymph node draining the injection site, which further increased the activation of Ag-specific T cells. AS04 was also found to directly stimulate those APCs in vitro but not directly stimulate CD4+ T or B lymphocytes. These AS04-induced innate responses were primarily due to MPL. Aluminum salt appeared not to synergize with or inhibit MPL, but rather it prolonged the cytokine responses to MPL at the injection site. Altogether these results support a model in which the addition of MPL to aluminum salt enhances the vaccine response by rapidly triggering a local cytokine response leading to an optimal activation of APCs. The transient and confined nature of these responses provides further supporting evidence for the favorable safety profile of AS04 adjuvanted vaccines.

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“…The adjuvant activities of TLR agonists are usually a manifestation of multiple effects on the antigen presentation-effector apparatus. 55 For instance, monophosphoryl lipid A induces dendritic cell maturation, [56][57][58][59][60] upregulates MHC Class II molecules and CD80 and CD86, [61][62][63] and also indirectly reduces the threshold for activation of T H 1 cells. [64][65][66][67][68][69] …”

Section: Tlr4 Agonists-lipopolysaccharide Monophosphoryl Lipid a Andmentioning

confidence: 99%

“…99 In addition, PAM 2 CSK 4 and MALP-2 induce isotypic switching and differentiation of naïve human B lymphocytes to IgG-secreting plasma cells, 100 indicating a functional association between BCR stimulation and TLR activation. 100 Triacyl PAM 3 CSK 4 has been shown to dramatically enhance MHC Class I-restricted CTL proliferation to an immunodominant influenza peptide Mx [58][59][60][61][62][63][64][65][66] in a human autologous DC/CD8 + T cell co-culture model. 101 The peptide-specific CTLs (assessed by tetramer staining) were also found to be strong producers of IFNγ.…”

Section: Tlr1/tlr2/tlr6 Agonistic Bacterial Lipoteichoic Acid and Lipmentioning

confidence: 99%

Potential adjuvantic properties of innate immune stimuli

et al. 2009

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Just as the prescient comment by Gaston Ramon was relegated to the last footnote of his 1926 paper, 1 so has research on the mechanisms of action of adjuvants, until recently, languished as parenthetical annotations and addenda in the archives of immunology and vaccine development. Ramon defined immunological adjuvants as "substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone." Interestingly enough, he was referring to his empirical findings that the addition of bread crumbs, tapioca, saponin and 'starch oil' to antigenic preparations greatly enhanced antibody responses to diphtheria or tetanus. 2 A year later, the adjuvanticity of aluminum salts (primarily phosphate and hydroxide) was discovered by Glenny and coworkers. 3 In the 83 years that have elapsed, the repertoire of investigational adjuvants has grown to encompass a very wide range of materials, 4 but aluminum salt-based mineral salts (generically, and incorrectly, termed "alum") have remained the only adjuvants currently approved by the FDA. Aluminum salts have enjoyed a good safety record, but they are weak adjuvants for antibody induction and induce a T helper-2 (T H 2)-skewed, rather than a T helper-1 (T H 1) response. 5,6 Furthermore, not only are aluminum salts ineffective at inducing cytotoxic T lymphocyte (CTL) or mucosal IgA antibody responses, but also have a propensity to induce IgE responses, which have been associated with allergic reactions in some subjects. 5,6 Very recent reports implicate the Nalp3 inflammasome, a component of the innate immune response, as the effector limb of alum-associated adjuvanticity. [7][8][9] In 1962, Dresser observed that injection of purified soluble proteins not only failed to stimulate an immune response, but tolerized animals unless a bacterial extract was admixed with the protein immunogen. 10 This led him to redefine adjuvanticity as "a property of a substance which can act as a physiological switch, directing at least some immunologically competent cells to respond by making antibody rather than by becoming immunologically paralyzed by the antigen," 11 confirming Johnson's earlier observations that lipopolysaccharide (LPS) from Gram-negative bacteria exerted potent adjuvant properties, 12 and perhaps paved the way for the subsequent discovery of the wide range of microorganism-derived adjuvants. 13 TLRs are pattern recognition receptors present on diverse cell types that recognize specific molecular patterns present in molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). 14,15 There are 10 TLRs in the human genome;

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Role of CD80 and CD86 in host immune responses to the recombinant hemagglutinin domain of Porphyromonas gingivalis gingipain and in the adjuvanticity of cholera toxin B and monophosphoryl lipid A

Cited by 16 publications

References 47 publications

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

AS04, an Aluminum Salt- and TLR4 Agonist-Based Adjuvant System, Induces a Transient Localized Innate Immune Response Leading to Enhanced Adaptive Immunity

Potential adjuvantic properties of innate immune stimuli

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