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.
    Full-text · Article · Nov 2014 · Vaccine
    • "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.
    No preview · Article · Mar 2012 · European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences
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    • "The only vaccine adjuvant that is approved by the United States Food and Drug Administration (FDA) is alum (aluminum-based mineral salt) [6]. In addition to alum, the oil-in-water emulsions MF59 and AS03 and the monophosphoryl Lipid A formulated in alum (AS04) have been approved by the European Medicines Agency as vaccine adjuvants [6] [7] [8]. However, alum remains the only adjuvant approved worldwide for human use [9]. "
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    ABSTRACT: To determine the efficacy of the mixture of propranolol (PRP), a beta-adrenergic receptor antagonist, and alum, as a new adjuvant, in the induction of humoral and cellular immunity in response to heat-killed Salmonella typhimurium (S. typhimurium) (HKST) as a model vaccine. BALB/c mice were divided into five groups. Mice in the experimental groups received either the HKST vaccine alone or in combination with the adjuvant alum, PRP or the alum-PRP mixture. Mice in the negative control group received phosphate-buffered saline. All mice were immunized two times on days 0 and 14. Two weeks after the last immunization, immune responses to S. typhimurium were assessed. Administration of the alum-PRP mixture as an adjuvant increased the ability of the HKST vaccine to enhance lymphocyte proliferation, shifted the immune response towards a T-helper (Th) 1 pattern and increased S. typhimurium specific IgG, IgG2a and IgG1. This resulted in improved protective immunity against S. typhimurium. Administration of the alum-PRP mixture as an adjuvant in combination with the HKST vaccine, can enhance both humoral and cellular immunity and shift the immune responses to a Th1 pattern.
    Full-text · Article · Feb 2012 · Vaccine
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