The adjuvant effects of the toll-like receptor 3 ligand polyinosinic-cytidylic acid poly (I:C) on antigen-specific CD8+ T cell responses are partially dependent on NK cells with the induction of a beneficial cytokine milieu

Salem, Mohamed L.; El‐Naggar, Sabry A.; Kadima, Andre N.; Gillanders, William E.; Cole, David J.

doi:10.1016/j.vaccine.2006.04.010

Cited by 102 publications

(80 citation statements)

References 67 publications

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“…A synthetic and seemingly popular dsRNA is poly(I:C) (polyinosine-polycytidylic acid). The immune stimulatory effect of poly (I:C) is likely through activation of TLR3 [382,383], and possibly other receptors as well [380]. Stimulation of bone marrow-derived murine dendritic cell populations with poly(I:C) results in Th1-polarized maturation of dendritic cells in mice [92].…”

Section: Rna-like Compoundsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Rna-like Compoundsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…134 Poly(I:C) also induced functional CD8 + T-cell responses against OVA peptides in murine models; antigen-specific CD8 + responses were found not onto be strongly Type I IFN-dependent, 135 but also on the cytokine milieu provided by activated NK cells. 136 Although the strong adjuvantic properties of poly I:C have been validated in multiple immunization models including the induction of mucosal (IgA-mediated) immunity, [137][138][139][140][141][142] it remains to be seen whether the in vivo stability of poly(I:C) formulations would be sufficient to permit a detailed evaluation of its potential as an adjuvant in human trials.…”

Section: Intracellular Tlr3 Activation: Dsrna and Poly (I:c)mentioning

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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“…In another study, antibody responses to a hepatitis vaccine were significantly increased when animals were immunized with antigen in CpG ODN plus liposomes as adjuvant, as opposed to immunization with antigen and CpG ODN alone (93). It was also shown that the effectiveness of poly I:C as a vaccine adjuvant could be substantially improved by incorporation of liposome complexes in the vaccine (94). Finally, it was also shown that complexes of cationic liposomes and poly I:C were effective for tumor immunotherapy and induction of tumor-specific CD8 + T cell responses (95).…”

Section: Cationic Liposomes-nucleic Acid Complexes As Vaccine Adjuvantsmentioning

confidence: 99%

Liposome–nucleic acid immunotherapeutics

Dow¹

2007

Expert Opinion on Drug Delivery

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Cationic liposome-nucleic acid complexes, which were originally developed for use as non-viral gene delivery vectors, may now have an equally important application as immunotherapeutic drugs. Recent studies have highlighted the ability of cationic liposomes to markedly potentiate activation of the innate immune system by certain Toll-like receptor (TLR) agonists. The immune enhancing properties of cationic liposomes are most obvious when they are combined with nucleic acid agonists for endosomally-located TLRs, including TLR3, TLR7/8, and TLR9. How this immune potentiation by cationic liposomes is mediated is not completely understood, but is thought to reflect the combined effects of more efficient endosomal targeting, protection from extracellular degradation, and signaling through newly identified cytoplasmic receptors for nucleic acids. The potent innate immune stimulatory properties of liposome-nucleic acid complexes make them particularly effective as immunotherapeutics or vaccine adjuvants. As stand-alone immunotherapeutics, liposome-nucleic acid complexes have demonstrated impressive anti-cancer activity in a number of different animal tumor models. Moreover, liposome-nucleic acid complexes also show promise for immunotherapy of acute viral and bacterial infections and chronic fungal infections. When used as vaccine adjuvants, liposome-nucleic acid complexes target antigens for efficient uptake by dendritic cells and are particularly effective in eliciting T cell responses. Thus, cationic liposomes combined with nucleic acids form the basis for a potent and versatile immunotherapeutic platform.

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The adjuvant effects of the toll-like receptor 3 ligand polyinosinic-cytidylic acid poly (I:C) on antigen-specific CD8+ T cell responses are partially dependent on NK cells with the induction of a beneficial cytokine milieu

Cited by 102 publications

References 67 publications

Selection of Adjuvants for Enhanced Vaccine Potency

Selection of Adjuvants for Enhanced Vaccine Potency

Potential adjuvantic properties of innate immune stimuli

Liposome–nucleic acid immunotherapeutics

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