MF59 Design and Evaluation of a Safe and Potent Adjuvant for Human Vaccines

G, Ott; Gl, Barchfeld; Chernoff, David; Radhakrishnan, R.; P, van Hoogevest; G, Van Nest

doi:10.1007/978-1-4615-1823-5_10

Cited by 258 publications

(175 citation statements)

References 26 publications

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“…Montanide ISA720, a metabolizable oil adjuvant (Seppic Inc. Fairfield, NJ) [29]; MF59, squalene/oil emulsion (Chiron Corp. Emeryville, CA) [30]; QS21, a saponin derivative (Antigenics Inc. Lexington, MA) [31]; MPL (from E. coli F583 Rd mutant, Sigma-Aldrich, St Louis, MO); MPL-AF, monophosphoryl lipid A in aqueous formulation (Corixa Inc. Seattle, WA) [32]; MPL-SE, monophosphoryl lipid A in squalene emulsion (Corixa Inc. Seattle WA) [33]; and Freund's Adjuvants, CFA/IFA (Gibco, Grand Island, NY). Additional formulations comprised of combinations of above adjuvants were also used, ISA720/MPL, ISA720/QS21, ISA720/QS21/MPL.…”

Section: Adjuvant Formulationsmentioning

confidence: 99%

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Hui

Hashimoto

2007

Vaccine

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The efficacy of vaccine adjuvants can be influenced by the immunological environment of the host, depending on the mechanism(s) by which they exert their immunopotentiating activities. Interleukin-6 is a pleiotropic cytokine that has a broad range of biological activities on immune and non-immune cells. We investigated the role of IL-6 on the ability of nine adjuvant formulations to induce antibody responses to the P. falciparum MSP1-19 malaria vaccine, using IL-6 -/-(KO) mice. Results showed that some adjuvants, ie. MPL-SE, CFA/IFA, ISA720/QS21/MPL, depended on IL-6 for their efficacy, while others exhibited increased potency in its absence. The efficacy of adjuvants in the IL-6 KO environment cannot be solely attributed to their ability to stimulate antigen-specific cellular responses, suggesting that other biological activities of IL-6 are also important. The results further suggest that two adjuvants utilized dissimilar pathways to potentiate the same type of immune response.

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Section: Adjuvant Formulationsmentioning

confidence: 99%

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Hui

Hashimoto

2007

Vaccine

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“…We propose that the PorB porin from commensal N. Lactamica acts as an immune adjuvant and has the potential of being developed as a potent immune modulator derived from a non-pathogenic bacterium, which would positively affect ease of manufacturing. Examples of adjuvants are oil emulsions [4][5][6], squalene (MF59) [7], immune stimulating complexes (ISCOMs [8,9]) with Quil-A and both gram-negative bacteria and bacterial products [4,[10][11][12]. These include DNA with immunostimulatory CpG motifs (one of the most powerful adjuvants [13]), Bordetella pertussis toxin [2,14], Corynebacterium granulosum derived P40 component [15], MPL [16], Mycobacterium and its components (Freund adjuvant) [4,17], Cholera toxin [18] and porins from various organisms such as Fusobacterium nucleatum [19], Shigella [20][21][22], Salmonella [22,23] and Neisseria meningitidis and gonorrhoeae [24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Liu

Wetzler

Massi

2008

Vaccine

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Porins from pathogenic Neisseriae are among several bacterial products with immune adjuvant activity. N. meningitidis (Nme) PorB, has been shown to induce immune cells activation in a TLR2-dependent manner and acts as a vaccine immune adjuvant. The PorB porin from Neisseria lactamica (Nlac), a common nasopharyngeal commensal shares significant structural and functional similarities with Nme PorB. In this work we ask whether the immune adjuvant ability of porins from pathogenic Neisserial strains is a characteristic shared with porins from non-pathogenic Neisserial species or whether it is unique for bacterial products derived from microorganisms capable of inducing inflammation and disease. We evaluate the potential immune adjuvant effect of Nlac PorB in mice using ovalbumin (OVA) as a prototype antigen. Immunization with Nlac PorB/OVA induced high OVA-specific IgG and IgM titers compared to OVA alone, similar to other adjuvants such as Nme PorB and alum. High titers of IgG1 and IgG2b were detected as well as production of IL-4, IL-10, IL-12 and INF-γ in response to Nlac PorB, consistent with induction of both a Th1-type and a Th2-type immune response. OVA-specific proliferation was also determined in splenocytes from Nlac PorB/OVA immunized mice. In addition, B cell activation in vitro and cytokine production in response to Nlac PorB was found to be mediated by TLR2, in a similar manner to Nme PorB.

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“…We conducted a phase II study wherein healthy adults received 2 doses of a subunit H5N1 A/Vietnam/1194/2004 vaccine as prepandemic vaccination, followed at 6 months by a third booster dose. The vaccine was either plain (Non-Adj-15) or adjuvanted with MF59 (MF59-H5N1), an oil/water proprietary adjuvant used in seasonal flu vaccines since 1997 (11,12).…”

mentioning

confidence: 99%

Adjuvanted H5N1 vaccine induces early CD4⁺T cell response that predicts long-term persistence of protective antibody levels

Galli

Medini

Borgogni

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

238

173

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Immune responses to vaccination are tested in clinical trials. This process usually requires years especially when immune memory and persistence are analyzed. Markers able to quickly predict the immune response would be very useful, particularly when dealing with emerging diseases that require a rapid response, such as avian influenza. To address this question we vaccinated healthy adults at days 1, 22, and 202 with plain or MF59-adjuvanted H5N1 subunit vaccines and tested both cell-mediated and antibody responses up to day 382. Only the MF59-H5N1 vaccine induced high titers of neutralizing antibodies, a large pool of memory H5N1-specific B lymphocytes, and H5-CD4 ؉ T cells broadly reactive with drifted H5. The CD4 ؉ response was dominated by IL-2 ؉ IFN-␥ ؊ IL-13 ؊ T cells. Remarkably, a 3-fold increase in the frequency of virus-specific total CD4 ؉ T cells, measurable after 1 dose, accurately predicted the rise of neutralizing antibodies after booster immunization and their maintenance 6 months later. We suggest that CD4 ؉ T cell priming might be used as an early predictor of the immunogenicity of prepandemic vaccines.H5N1 influenza vaccine ͉ MF59 adjuvant ͉ prepandemic vaccination ͉ immune memory ͉ protection

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MF59 Design and Evaluation of a Safe and Potent Adjuvant for Human Vaccines

Cited by 258 publications

References 26 publications

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Adjuvanted H5N1 vaccine induces early CD4⁺T cell response that predicts long-term persistence of protective antibody levels

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MF59 Design and Evaluation of a Safe and Potent Adjuvant for Human Vaccines

Cited by 258 publications

References 26 publications

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Adjuvanted H5N1 vaccine induces early CD4+T cell response that predicts long-term persistence of protective antibody levels

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Adjuvanted H5N1 vaccine induces early CD4⁺T cell response that predicts long-term persistence of protective antibody levels