Guy, B. The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol 5: 505-517

Research Department, sanofi pasteur, Campus Merieux, 69280 Marcy l'Etoile, France.
Nature Reviews Microbiology (Impact Factor: 23.57). 08/2007; 5(7):505-17. DOI: 10.1038/nrmicro1681
Source: PubMed


Developing efficient and safe adjuvants for use in human vaccines remains both a challenge and a necessity. Past approaches have been largely empirical and generally used a single type of adjuvant, such as aluminium salts or emulsions. However, new vaccine targets often require the induction of well-defined cell-mediated responses in addition to antibodies, and thus new immunostimulants are required. Recent advances in basic immunology have elucidated how early innate immune signals can shape subsequent adaptive responses and this, coupled with improvements in biochemical techniques, has led to the design and development of more specific and focused adjuvants. In this Review, I discuss the research that has made it possible for vaccinologists to now be able to choose between a large panel of adjuvants, which potentially can act synergistically, and combine them in formulations that are specifically adapted to each target and to the relevant correlate(s) of protection.

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Available from: Bruno Guy, Jul 30, 2014
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    • "Adults worms of F. hepatica adult worm secrete a variety of molecules that direct the immune response towards a favourable non-protective Th2-mediate/regulatory environment, like the excretory secretory antigens of F. hepatica which have been widely studied by Dalton et al. (2013). Adjuvants can influence the T-helper cell polarisation creating bias towards Th1 or Th2 immune responses (Guy 2007), but some adjuvant substances have toxic or undesirable side effects. Hence, seeking for non-toxic adjuvants is an important task. "
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    ABSTRACT: We have studied the influence of both levamisole (AL) and Freund's adjuvant (AF) on the immunisation of mice with the secretory antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758. Total IgG antibodies were detected in all groups where the F. hepatica antigen was administered, been levels of IgG1 increased respect to IgG2a antibodies. During immunisation, IL-4 and IFN-γ were only detected in AL and AF groups, but after infection, IL-4 boosted in all groups. IFN-γ increased two fold in AF and AL groups compared to the saline solution (AS) group. Worm recovering was of 32-35% in groups administered without antigen whereas in AS, AL and AF groups recovering was of 25%, 12% and 8%, respectively. Macroscopical lesions in the liver were scarce in AL and AF groups. Our data suggest that immunisation of mice with antigens of F. hepatica enhances the immune response avoiding both liver damage and worm establishment after challenge infection. The murine model of fasciolosis has appeared to be useful to elucidate the mechanism by which the parasite modulates immune responses toward a Th2 type but also the development of Th1 type-inducing vaccines.
    Folia parasitologica 08/2015; 62. DOI:10.14411/fp.2015.047 · 1.15 Impact Factor
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    • "New adjuvants based on nanospheres, microspheres or microparticles have been developed, and some have induced a good immune response with less damage than associated with oil-based adjuvants [6e9]. Some oil-based adjuvants, such as those formed by Freund's adjuvant , Montanide ISA51 or ISA720, are used to form water-in-oil emulsions in which aqueous droplets containing the antigen are dispersed in the oily phase [10]. These droplets are of different sizes, and the larger ones cannot be phagocytosed and transported from the peritoneal cavity to lymphoid organs [6], remaining at the site of injection until they have disintegrated. "
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    ABSTRACT: New adjuvants based on microparticles are being developed for use in fish vaccines. The size of the microparticles may affect the immune response generated, as the adjuvant can either be retained at the site of injection or transported to lymphoid organs. The objectives of this study were to evaluate the maximum size of particles that can be exported out of the cavity, to determine the phagocytosis kinetics and to establish the routes whereby particle-containing cells move from the peritoneal cavity after injection. Fish were injected intraperitoneally with fluorescent cyclodextrins or with fluorescent particles of different size (0.1 - 10 μm). Phagocytes containing beads of size 4 μm or larger did not reach lymphoid organs, although some were able to cross the peritoneal mesothelium. The number of free peritoneal neutrophils and macrophage-like cells containing beads peaked at 6 and 24 h respectively, and the numbers then decreased quickly, indicating migration of cells to the peritoneum or other body areas. Migration of cells containing beads mainly occurs through the visceral peritoneum. These cells were found on the latero-ventral surfaces of the peritoneal folds that connect the visceral organs. Except for some vascularised areas, the surfaces of liver, stomach and intestine were devoid of particle-containing cells. Some cells containing beads were also found attached to the parietal peritoneum, although in lower numbers than in the visceral peritoneum. Such cells were also found in high numbers in the spleen and kidney 6 h post injection. Because cells containing phagocytosed material quickly become attached to the peritoneum or migrate to lymphoid organs, the immune response generated by a vaccine or by an inflammatory stimulus should probably be evaluated in attached cells as well as in free peritoneal cells. Copyright © 2015. Published by Elsevier Ltd.
    Fish &amp Shellfish Immunology 03/2015; 44(2). DOI:10.1016/j.fsi.2015.03.034 · 2.67 Impact Factor
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    • "However, in comparison to traditional vaccines based on live attenuated and whole inactivated pathogens, recombinant antigens are commonly associated with reduced immunogenicity due to their lack of intrinsic immunostimulatory capacity. Hence adjuvants are required in the vaccine formulation to potentiate the immune response against co-administered antigen(s) thereby enhancing vaccine efficacy [1] [2]. "
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    ABSTRACT: Linking physicochemical characterization to functional properties is crucial for defining critical quality attributes during development of subunit vaccines toward optimal safety and efficacy profiles. We investigated how the trehalose 6,6′-diester (TDX) chain length influenced the physicochemical and immunopotentiating properties of the clinically tested liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and analogues of trehalose-6,6′-dibehenate (TDB). TDB analogues with symmetrically shortened acyl chains [denoted X: arachidate (A), stearate (S), palmitate (P), myristate (Myr) and laurate (L)] were incorporated into DDA liposomes and characterized with respect to size, polydispersity index, charge, thermotropic phase behavior and lipid-lipid interactions. Incorporation of 11 mol% TDX into DDA liposomes significantly decreased the polydispersity index when TDA, TDS, TDP and TDMyr were incorporated, whereas both the initial size and the charge of the liposomes were unaffected. The long-term colloidal stability was only decreased when including TDL in DDA liposomes. The fatty acid length of TDX affected the phase transition of the liposomes, and for the DDA/TDP and DDA/TDS liposomes a homogeneous distribution of the lipids in the bilayer was indicated. The membrane packing was studied further by using the Langmuir monolayer technique. Incorporation of TDS improved the packing of the lipid monolayer, as compared to the other analogues, suggesting the most favorable stability. Finally, immunization of mice with the recombinant tuberculosis fusion antigen Ag85B-ESAT-6-Rv2660c (H56) and the physicochemically most optimal formulations (DDA/TDB, DDA/TDS and DDA/TDP) induced comparable T-cell responses. In conclusion, of the investigated TDB analogues, incorporation of 11 mol% TDS or TDP into DDA liposomes resulted in an adjuvant system with the most favorable physicochemical properties and an immunological profile comparable to that of DDA/TDB.
    European Journal of Pharmaceutics and Biopharmaceutics 11/2014; DOI:10.1016/j.ejpb.2014.10.015 · 3.38 Impact Factor
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