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/
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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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Article: New horizons in adjuvants for vaccine development. Trends Immunol

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    • "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.
    Immunological Investigations 10/2015; 44(7):627-642. DOI:10.3109/08820139.2015.1070268 · 1.99 Impact Factor
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    • "Vaccination has arguably been the most successful and effective medical intervention for preventing infectious diseases, resulting in decreased mortality, extended life expectancy, and improved quality of life [1] [2] [3]. More than 600 million vaccine formulations are now administered by subcutaneous or intramuscular injections, according to WHO records [4]. "
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    ABSTRACT: Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials. In this review, the state of art of chitosan and its derivatives as mucosal adjuvants, including thermo-sensitive chitosan system as mucosal adjuvant that were newly developed by author's group, was described, as well as the clinical application perspective. After a brief introduction of mucosal adjuvants, chitosan and its derivatives as robust immune potentiator were discussed in detail and depth, in regard to the metabolism, safety profile, mode of actions and preclinical and clinical applications, which may shed light on the massive clinical application of chitosan as mucosal adjuvant. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 08/2015; 33(44). DOI:10.1016/j.vaccine.2015.07.101 · 3.62 Impact Factor
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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.
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