Vaccine adjuvants: role and mechanisms of action in vaccine immunogenicity

Marciani, Dante J.

doi:10.1016/s1359-6446(03)02864-2

Cited by 247 publications

(168 citation statements)

References 69 publications

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“…Liposomes have also been used to introduce protein Ags into the cytosol and the MHC class I pathway for generating CD8 ϩ T cell responses (10,25,26). However, cationic liposomes alone are relatively inert in terms of activating innate immune responses (16,27,28).…”

Section: S Timulation Of Innate Immunity Is Necessary For Generationmentioning

confidence: 99%

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Zaks

Jordan

Guth³

et al. 2006

The Journal of Immunology

227

187

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Complexing TLR9 agonists such as plasmid DNA to cationic liposomes markedly potentiates their ability to activate innate immunity. We therefore reasoned that liposomes complexed with DNA or other TLR agonists could be used as effective vaccine adjuvants. To test this hypothesis, the vaccine adjuvant effects of liposomes complexed to TLR agonists were assessed in mice. We found that liposomes complexed to nucleic acids (liposome-Ag-nucleic acid complexes; LANAC) were particularly effective adjuvants for eliciting CD4+ and CD8+ T cell responses against peptide and protein Ags. Notably, LANAC containing TLR3 or TLR9 agonists effectively cross-primed CD8+ T cell responses against even low doses of protein Ags, and this effect was independent of CD4+ T cell help. Ag-specific CD8+ T cells elicited by LANAC adjuvants were functionally active and persisted for long periods of time in tissues. In a therapeutic tumor vaccine model, immunization with the melanoma peptide trp2 and LANAC adjuvant controlled the growth of established B16 melanoma tumors. In a prophylactic vaccine model, immunization with the Mycobacterium tuberculosis protein ESAT-6 with LANAC adjuvant elicited significant protective immunity against aerosol challenge with virulent M. tuberculosis. These results suggest that certain TLR agonists can be combined with cationic liposomes to produce uniquely effective vaccine adjuvants capable of eliciting strong T cell responses against protein and peptide Ags.

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Section: S Timulation Of Innate Immunity Is Necessary For Generationmentioning

confidence: 99%

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Zaks

Jordan

Guth³

et al. 2006

The Journal of Immunology

227

187

View full text Add to dashboard Cite

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“…It is worth noting that the mechanism by which saponin potentiates an immune response remains unclear. Hypotheses have been raised about whether saponin, through lectin-mediated cell membrane interactions, could facilitate the uptake of the antigen into antigen-presenting cells, leading to specific cytokine profiles that enhance T and/or B-cell responses (Kensil 1996, Marciani 2003, Adams et al 2010.…”

mentioning

confidence: 99%

Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production

Grenfell

Silva

Testasicca

et al. 2010

Mem. Inst. Oswaldo Cruz

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This study evaluated two vaccine candidates for their effectiveness in protecting BALB/c mice against Leishmania chagasiinfection. These immunogenic preparations were composed of Leishmania amazonensisor Leishmania braziliensisantigenic extracts in association with saponin adjuvant. Mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of L. chagasiby intravenous injection. We observed that both vaccine candidates induced a significant reduction in the parasite load of the liver, while the L. amazonensisantigenic extract also stimulated a reduction in spleen parasite load. This protection was associated with a suppression of both interleukin (IL)-10 and IL-4 cytokines by spleen cells in response to L. chagasiantigen. No change was detected in the production of IFN-γ. Our data show that these immunogenic preparations reduce the type 2 immune response leading to the control of parasite replication

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“…E ffective vaccines against bacterial capsular polysaccharide (CPS) 3 Ags appear to require three components: 1) a CPS B cell epitope to induce the production of Ab that mediates opsonin-dependent phagocytosis and bacterial clearance; 2) a T cell epitope to induce T cell help for an IgG isotype switch and immune memory; and 3) an adjuvant to provide an Ag depot or a suitable cytokine environment (1). Classical adjuvants often contain bacterial or other ligands that stimulate TLR signaling of innate immune cells (2).…”

mentioning

confidence: 99%

Pneumococcal Capsular Polysaccharide Is Immunogenic When Present on the Surface of Macrophages and Dendritic Cells: TLR4 Signaling Induced by a Conjugate Vaccine or by Lipopolysaccharide Is Conducive

Cohen¹,

Stolarsky-Bennun²,

Amir-Kroll³

et al. 2008

The Journal of Immunology

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Previously, we reported that a peptide, p458, from the sequence of the mammalian 60-kDa heat shock protein (hsp60) molecule can serve as a carrier in conjugate vaccines with capsular polysaccharide (CPS) molecules of various bacteria. These conjugate vaccines were effective injected in PBS without added adjuvants. We now report that p458 conjugated to pneumococcal CPS type 4 (PS4) manifests innate adjuvant effects: it stimulated mouse macrophages to secrete IL-12 and induced the late appearance of PS4 on the macrophage surface in a TLR4-dependent manner; PS4 alone or conjugated to other carriers did not stimulate macrophages in vitro. The injection of macrophages manifesting PS4 on the surface into mice induced long-term resistance to lethal Streptococcus pneumoniae challenge. The TLR4 ligand LPS could also induce the late appearance on the surface of unconjugated PS4 and resistance to challenge in injected mice. Resistance was not induced by macrophages containing only internalized PS4 or by pulsed macrophages that had been lysed. Glutaraldehyde-fixed macrophages pulsed with PS4 did induce resistance to lethal challenge. Moreover, bone marrow-derived dendritic cells activated by LPS and pulsed with unconjugated CPS were also effective in inducing resistance to lethal challenge. Resistance induced by the PS4-pulsed bone marrow-derived dendritic cell was specific for pneumococcal CPS serotypes (type 3 or type 4) and was associated with the induction of CPS-specific IgG and IgM Abs.

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Vaccine adjuvants: role and mechanisms of action in vaccine immunogenicity

Cited by 247 publications

References 69 publications

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production

Pneumococcal Capsular Polysaccharide Is Immunogenic When Present on the Surface of Macrophages and Dendritic Cells: TLR4 Signaling Induced by a Conjugate Vaccine or by Lipopolysaccharide Is Conducive

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