Vaccine adjuvants: The dream becomes real

ALTA R&D in Biotechnology, Siena, Italy.
Human vaccines (Impact Factor: 3.64). 07/2008; 4(5):347-9. DOI: 10.4161/hv.4.5.6438
Source: PubMed


After about 70 years two new adjuvants have been approved for human vaccines. The first is MF59 developed by the ex-Chiron now Novartis Vaccines and it consists in an oil-in-water emulsion, comprising a low content of biodegradable squalene oil (4.3%) as the dispersed phase, which is stabilized by two non-ionic surfactants (Tween 80 and Span 85), and a low ionic strength citrate buffer as the continuous phase. The second one, defined as AS04, has been developed by GSK Biologics and consists in 3-0-desacyl-4'-monophosphoryl lipid A (MPL) that comes from the cell wall LPS of Gram-negative Salmonella minnesota R595 and is detoxified by mild hydrolytic treatment and purification. It is absorbed on aluminum hydroxide or aluminum phosphate. Thus, new molecules are available to improve the immune response to vaccines also in humans: this is the beginning of a new era in vaccinology.

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Available from: Aldo Tagliabue, Sep 28, 2014
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    • "Monophosphoryl lipid A (MPL) and aluminum hydroxide (alum) are two adjuvants approved for use in human vaccines. MPL, a lipopolysaccharide derivative from Salmonella minnesota R595 [26] [27], is immunostimulatory because of toll-like receptor-4 agonist activity [27] and is licensed for use in a human papillomavirus vaccine. "
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    ABSTRACT: Two major antigenically heterogenous norovirus genogroups (GI and GII) commonly infect humans and are the leading cause of foodborne, viral gastrointestinal infections in adults.Methods We assessed B cell responses in participants in a double-blind, placebo-controlled, dose-escalation phase 1 study of the safety and immunogenicity of an intramuscular bivalent norovirus virus-like particle (VLP) vaccine. The vaccine contained a GI.1 VLP (Norwalk) and a consensus GII.4 VLP, representing the two major genotypes that cause human disease, and was administered on days 0 and 28 to healthy adults aged 18–49 years. Four separate cohorts received increasing doses of 5 μg, 15 μg, 50 μg, and 150 μg of each VLP adjuvanted in monophosphoryl lipid A and alum. PBMCs were analyzed for B cell activation and mucosal homing markers (flow cytometry) and VLP-specific and total IgG and IgA Ab-secreting cells (ASCs); and serum titers of VLP-specific IgG, IgA, and Pan-Ig were determined.ResultsThe vaccine elicited CD27+ CD38+ plasmablasts and high frequencies of ASCs specific for both VLP antigens in the peripheral blood at 7 days after the first dose. The plasmablasts exhibited a mucosal-homing phenotype and included a high proportion of IgA ASCs. Serum antibodies increased as early as 7 days after the first immunization.Conclusions The data suggest that a single dose of the IM bivalent norovirus vaccine is effective in activating pre-existing B cell memory. The rapid B cell response and the mucosal homing phenotype of induced ASCs are consistent with anamnestic responses in subjects primed by prior oral norovirus infection.This study is registered at Identifier NCT01609257.
    Vaccine 11/2014; 33(4). DOI:10.1016/j.vaccine.2014.09.073 · 3.62 Impact Factor
    • "The field of adjuvants is rapidly evolving. Whereas alum has been the only approved adjuvant for many years, vaccines containing emulsion-based adjuvants (MF59) and the LPS derivate monophosphoryl lipid A (in AS04) (Tagliabue and Rappuoli, 2008) have been licensed for use in Europe since 1997 and 2005, respectively. Moreover, increased knowledge on the activation of the innate immune system has led to the identification of new adjuvants that activate APCs specifically via TLRs (Pasare and Medzhitov, 2005) or NOD-like receptors (NLRs). "
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    ABSTRACT: N-trimethyl chitosan (TMC) nanoparticles have been shown to increase the immunogenicity of subunit antigens after nasal and intradermal administration. This work describes a second generation of TMC nanoparticles containing ovalbumin as a model antigen (TMC/OVA nanoparticles) and an immunopotentiator (TMC/OVA/immunopotentiator nanoparticles). The selection of immunopotentiators included Toll-like receptor (TLR) ligands lipopolysaccharide (LPS), PAM(3)CSK(4) (PAM), CpG DNA, the NOD-like receptor 2 ligand muramyl dipeptide (MDP) and the GM1 ganglioside receptor ligand, cholera toxin B subunit (CTB). The TMC/OVA/immunopotentiator nanoparticles were characterised physico-chemically and their immunogenicity was assessed by determining the serum IgG, IgG1, IgG2a titres and secretory IgA levels in nasal washes after intradermal and nasal vaccination in mice. After nasal vaccination, TMC/OVA nanoparticles containing LPS or MDP elicited higher IgG, IgG1 and sIgA levels than non-adjuvanted TMC/OVA particles, whereas nanoparticles containing CTB, PAM or CpG did not. After intradermal vaccination, the TMC/OVA/CpG and TMC/OVA/LPS nanoparticles provoked higher IgG titres than plain TMC/OVA particles. Altogether, our results show that co-encapsulation of an additional immunopotentiator with the antigen into TMC nanoparticles can further improve the immunogenicity of the vaccine. However, the strength and quality of the response depends on the immunopotentiator as well as the route of administration.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 03/2012; 45(4):475-81. DOI:10.1016/j.ejps.2011.10.003 · 3.35 Impact Factor
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    • "Basically, immunologic adjuvants are substances, administered in conjunction with the vaccine, which stimulate the immune system and increase the host response. The most common adjuvant comprising squalene is MF59, developed by the ex-Chiron now Novartis Vaccines, which consists in an oil-in-water emulsion, comprising a low content of biodegradable squalene oil (4.3%) as the dispersed phase, which is stabilized by two non-ionic surfactants (Tween 80 and Span 85), and a low ionic strength citrate buffer as the continuous phase [3]. Although the definitive mechanisms supporting MF59 adjuvanticity are still unclear, previous studies (reviewed by Schultze et al.) showed that MF59administration (i) produces a significant influx of macrophages at the site of injection, a process which is associated with enhanced production of chemokines in cells resident at the injection site, and (ii) induces a strong T-cell response to a variety of different antigens, including bacterial toxins, outer membrane vesicles, polysaccharide conjugates, recombinant and viral antigens (e.g., influenza antigens) [4]. "
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    ABSTRACT: Squalene, a hydrocarbon obtained for commercial purposes primarily from shark liver oil and other botanic sources, is increasingly used as an immunologic adjuvant in several vaccines, including seasonal and the novel influenza A (H1N1) 2009 pandemic flu vaccines. Nearly a decade ago, squalene was supposed to be the experimental anthrax vaccine ingredient that caused the onset of Persian Gulf War syndrome in many veterans, since antibodies to squalene were detected in the blood of most patients affected by this syndrome. This evidence has raised a widespread concern about the safety of squalene containing adjuvants (especially MF59) of influenza vaccines. Nevertheless, further clinical evidence clearly suggested that squalene is poorly immunogenic, that low titres of antibodies to squalene can be also detected in sera from healthy individuals, and that neither the presence of anti-squalene antibodies nor their titre is significantly increased by immunization with vaccines containing squalene (or MF59) as an adjuvant. This review summarizes the current scientific evidence about the relationship between squalene, anti-squalene antibodies and vaccination.
    European Journal of Internal Medicine 04/2010; 21(2):70-3. DOI:10.1016/j.ejim.2009.12.001 · 2.89 Impact Factor
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