New horizons in adjuvants for vaccine development

Infectious Disease Research Institute, 1124 Columbia St. Suite 400, Seattle, WA 98104, USA.
Trends in Immunology (Impact Factor: 12.03). 01/2009; 30(1):23-32. DOI: 10.1016/
Source: PubMed

ABSTRACT 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, Aug 02, 2015
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    • "Alum has been widely used as an adjuvant for many antigens; however, it is not effective with all antigens [2]. An increasing number of studies have demonstrated disadvantages to using alum as an adjuvant; these include the necessity of cold-chain vaccine storage and distribution, and its unsuitability for lyophilization [3]. There are also side effects associated with alum-based vaccines, which include sterile abscesses, eosinophilia, and myofascitis, generally most of these serious side effects occur only in small percentages of those immunized [4]. "
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    ABSTRACT: Recombinant viral subunit-based vaccines have gained increasing attention due to their enhanced safety over the classic live-attenuated or inactivated vaccines. The low immunogenicity of the subunit antigen alone, however, requires the addition of an adjuvant to induce immunity. Particulate-based delivery systems have great potential for developing new vaccine adjuvants, compared to traditional aluminum-based saline adjuvants. The physicochemical properties of particulate vaccines have been extensively investigated; however, few studies have focused on how the administration route of various adjuvant-antigen combinations impacts the efficacy of the immune response. Here, for the first time, the viral Hepatitis B surface antigen (HBsAg) was combined with aluminum-based or cationic-microsphere (MP) based adjuvants to investigate the characteristics of immune responses elicited after immunization via the subcutaneous, intramuscular, or intraperitoneal routes respectively. In vitro, the MP-based vaccine significantly increased dendritic cell (DC) activation with up-regulated CD40 and CD80 expression and IL-12 production compared to alum-based vaccine. After immunization, both MP and alum-based vaccines produced increased IgG titers in mice. The administration route of these vaccines did influenced immune responses. The MP-based vaccine delivered via the intramuscular route yielded the highest levels of the IgG2a isotype. The alum-based vaccine, delivered via the same route, produced an IgG1-dominated humoral immune response. Moreover, subcutaneous and intramuscular immunizations with MP-based vaccine augmented Granzyme B, Th1-type cytokines (IL-2, IL-12, and IFN-gamma), and Th2 cytokine IL-4 secretions. These results demonstrate that MP-based vaccines have the capacity to induce higher cellular and humoral immune response especially via an intramuscular administration route than an alum-based vaccine.
    International Immunopharmacology 10/2014; 23(2). DOI:10.1016/j.intimp.2014.10.010 · 2.71 Impact Factor
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    • "In case of vaccines this co-stimulation is generated by the use of adjuvants that mimic the signals usually produced by natural pathogens. Currently only a few adjuvants are approved for human use e.g., MF59, alum (aluminum salts), Montanide ISA 51, Adjuvant System 04 (AS04), Adjuvant System 03 (AS03) and virosomes (Leroux-Roels 2010), (Reed et al., 2009), (Mbow et al., 2010). A limitation of such an approach to induce immunogenicity is that these adjuvants provide immunity by merely the stimulation of antibody production and do not potentiate the cellmediated immunity (Guy 2007). "
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    ABSTRACT: Nanogels have shown a great potential for the delivery of large number of drugs to different organs of the body owing to their high biocompatibility, high drug loading capacity, high biodegradability (and hence low cytotoxicity), good permeation capabilities and tissue mimicking properties. Their high water retention makes them ideal capable of incorporation of bulky drugs like proteins, peptides, oligonucleotides and other macromolecules. All these properties of nanogels make them able to carry number of drugs to vast number of organs. Nanogels have shown potential in many fields including chemotherapy, diagnosis, organ tergeting, gene delivery and many others. The main areas of the target for the nanogels have been tumors of brain, liver, skin etc. Other uses of the nanogel are in diabetes, inflammation, wound healing, local anesthesia etc. This review concentrates over the targeting potential of nanogels in different organs for various conditions.
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    • "The saponin-based adjuvants stimulate Th1 immune responses and production of CD8þ cytotoxic T-lymphocytes against antigens [13e15]. However, disadvantages including pain at the site of injection, severe local reactions and toxicity profile are associated with saponin-based adjuvants [16] [17]. Freund's complete adjuvant (FCA) is one of the most effective adjuvants, nevertheless, FCA is known to induce high toxicity and severe reactions [18]. "
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    ABSTRACT: Bovine Viral Diarrhoea Virus (BVDV) is widely distributed in cattle industries and causes significant economic losses worldwide annually. A limiting factor in the development of subunit vaccines for BVDV is the need to elicit both antibody and T-cell-mediated immunity as well as addressing the toxicity of adjuvants. In this study, we have prepared novel silica vesicles (SV) as the new generation antigen carriers and adjuvants. With small particle size of 50 nm, thin wall (∼6 nm), large cavity (∼40 nm) and large entrance size (5.9 nm for SV-100 and 16 nm for SV-140), the SV showed high loading capacity (∼ 250 μg/mg) and controlled release of codon-optimised E2 (oE2) protein, a major immunogenic determinant of BVDV. The in vivo functionality of the system was validated in mice immunisation trials comparing oE2 plus Quil A (50 μg of oE2 plus 10 μg of Quil A, a conventional adjuvant) to the oE2/SV-140 (50 μg of oE2 adsorbed to 250 μg of SV-140) or oE2/SV-140 together with 10 μg of Quil A. Compared to the oE2 plus Quil A, which generated BVDV specific antibody responses at a titre of 10(4), the oE2/SV-140 group induced a 10 times higher antibody response. In addition, the cell-mediated response, which is essential to recognise and eliminate the invading pathogens, was also found to be higher [1954-2628 spot forming units (SFU)/million cells] in mice immunised with oE2/SV-140 in comparison to oE2 plus Quil A (512-1369 SFU/million cells). Our study has demonstrated that SV can be used as the next-generation nanocarriers and adjuvants for enhanced veterinary vaccine delivery.
    Biomaterials 09/2014; 35(37). DOI:10.1016/j.biomaterials.2014.08.044 · 8.31 Impact Factor
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