New horizons in adjuvants for vaccine development. Trends Immunol

Infectious Disease Research Institute, 1124 Columbia St. Suite 400, Seattle, WA 98104, USA.
Trends in Immunology (Impact Factor: 10.4). 01/2009; 30(1):23-32. DOI: 10.1016/
Source: PubMed


Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now in licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to recombinant antigens has led many researchers to re-focus their vaccine development programs. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this review, we outline the current state of adjuvant research and development and how formulation parameters can influence the effectiveness of adjuvants.

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Available from: Sylvie Bertholet
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    • "Among the TLR agonists, TLR4 agonists hold particular promise effect as potential vaccine adjuvants for use in tumors immunotherapy[17]. The first TLR4 agonist approved for human use as a vaccine adjuvant is a chemically-modified natural lipid A product derived from the LPS of Salmonella Minnesota R595 and known as monophosphoryl lipid A (MPL)[18]. MPL is an effective adjuvant in prophylactic and therapeutic vaccines and presents an outstanding safety in humans[19,20]. α-Galactosylceramide (α-GalCer) represents another group of compounds that has shown to have an strong effect as vaccine adjuvant for immunotherapy of tumors[21]. "
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    ABSTRACT: DNA vaccines have emerged as an attractive approach for the generation of cytotoxic T lymphocytes (CTL). In our previous study, we found That Toll like receptor (TLR) ligands are promising candidates for the development of novel adjuvants for DNA vaccine. To improve the efficacy of DNA vaccine directed against human papillomavirus (HPV) tumors, we evaluated whether co-administration of a TLR4 ligand, monophosphoryl lipid A (MPL), and Natural Killer T Cell Ligand α-Galactosylceramide(α-GalCer) adjuvants with DNA vaccine would influence the anti-tumor efficacy of DNA vaccinations. We investigated the effectiveness of α-GalCer and MPL combination as an adjuvant with an HPV-16 E7 DNA vaccine to enhance antitumor immune responses. By using adjuvant combination for a DNA vaccine, we found that the levels of lymphocyte proliferation, CTL activity, IFN- γ, IL-4 and IL-12 responses, and tumor protection against TC-1 cells were significantly increased compared to the DNA vaccine with individual adjuvants. In addition, inhibition of IL-18 signaling during vaccination decreased IFN-γ responses and tumor protection, and that this inhibition suggested stimulatory role of IL-18 in adjuvant effects of α-GalCer and MPL combination. The strong adjuvanticity associated with α-GalCer/MPL combination may to be an important tool in the development of novel and strong cancer immunotherapy.
    Full-text · Article · Dec 2016 · Journal of Biomedical Science
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    • "Immune adjuvant plays an essential role in vaccine [6]. However, there are some deficiencies for commonly used adjuvant in clinic [7] [8]. Therefore, it is particularly important to develop new types of immune adjuvants. "
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    ABSTRACT: Objectives. The adjuvant activity of Epimedium polysaccharide-propolis flavone liposome (EPL) was investigated in vitro and in vivo. Methods. In vitro, the effects of EPL at different concentrations on splenic lymphocytes proliferation and mRNA expression of IFN- γ and IL-6 were determined. In vivo, the adjuvant activities of EPL, EP, and mineral oil were compared in BALB/c mice through vaccination with inactivated porcine circovirus type 2 (PCV2) vaccine. Results. In vitro, EPL promoted lymphocytes proliferation and increased the mRNA expression of IFN- γ and IL-6, and the effect was significantly better than EP at all concentrations. In vivo, EPL significantly promoted the lymphocytes proliferation and the secretion of cytokines and improved the killing activity of NK cells, PCV2-specific antibody titers, and the proportion of T-cell subgroups. The effects of EPL were significantly better than EP and oil adjuvant at most time points. Conclusion. EPL could significantly improve both PCV2-specific cellular and humoral immune responses, and its medium dose had the best efficacy. Therefore, EPL would be exploited in an effective immune adjuvant for inactivated PCV2 vaccine.
    Full-text · Article · Nov 2015 · Evidence-based Complementary and Alternative Medicine
    • "Liposomes function by fusing with the host cell membrane after phagocytosis and releasing the antigen into the cell cytoplasm after disruption by lysosomal phospholipases (Oussoren & Storm, 2001). This has led to the development of immunostimulatory complexes (ISCOMs) (Demana et al., 2004; Reed et al., 2009; Wilson-Welder et al., 2009). ISCOMs are plagued with tissue reactive hypersensitivity and haemolysis due to the incorporation of plant-derived saponins, which has impeded their use in humans (Wilson- Welder et al., 2009). "
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    ABSTRACT: Pheroid® technology was assessed as an alternative to Freund's adjuvant to raise antibodies in experimental animals. Chickens were immunized with two recombinantly expressed Plasmodium falciparum proteins, lactate dehydrogenase (PfLDH) and glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH), alone or in combination with Freund's adjuvant or Pheroid®. Chicken egg yolk antibodies (IgY) were isolated and compared for specificity, sensitivity and yield. Freund's adjuvant and Pheroid® stimulated prolonged antibody responses in chickens against both antigens. Affinity purified antibodies had specificity for the recombinant and the native proteins on Western blots. Antibodies generated in the presence of Freund's adjuvant had high sensitivity for both antigens. Pheroid® generated antibodies that detected the lowest concentration of recombinant PfLDH. Freund's adjuvant and Pheroid® both improved chicken IgY yields, with Pheroid® showing a 2-fold increase relative to controls. Pheroid® was well-tolerated in chickens and has potential for development as a safe adjuvant for testing alternative stimulatory factors to improve adjuvant formulations.
    No preview · Article · Oct 2015 · Immunological Investigations
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