Article

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: 23.32). 08/2007; 5(7):505-17. DOI: 10.1038/nrmicro1681
Source: PubMed

ABSTRACT 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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    • "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.
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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]. http://dx.doi.org/10.1016/j.ejpb.2014.10.015 "
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    European Journal of Pharmaceutics and Biopharmaceutics 11/2014; DOI:10.1016/j.ejpb.2014.10.015 · 4.25 Impact Factor
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    • "However, as results have shown, inclusion of DOPE alone in liposomal formulation (Lip-DOPE-P5) was not sufficient to elicit an effective immune response. Lip-DOPE-P5 formulation might have been able to deliver P5 antigen to MHC class I molecules successfully, however, once the peptide antigen was presented to CD8+ lymphocytes by APCs, presence of co-stimulatory molecules on the APCs was also required for activation of CD8 cells to produce CTLs [35] [36] [37]. MPL can induce intracellular signaling pathways leading to production of these co-stimulatory molecules through TLR4 stimulation [35]. "
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