The Adjuvant MF59: A 10-Year Perspective

Fang, Juanzhi; Hora, Maninder

doi:10.1385/1-59259-083-7:211

Cited by 48 publications

(45 citation statements)

References 18 publications

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“…However, vaccine development usually focuses on the induction of humoral immune responses, which has led to the development of adjuvants with the ability to enhance antibody responses. Specifically, aluminum salts (20) and oil-in-water emulsion MF59 (28), known to stimulate only humoral responses, are the most important available licensed adjuvants for humans. Consequently, most current vaccines failed to elicit significant Th1 responses or CTLs (19), which may be required to neutralize escape mechanisms from microbes and cancer cells.…”

mentioning

confidence: 99%

Proteasome-Independent Major Histocompatibility Complex Class I Cross-Presentation Mediated by Papaya Mosaic Virus-Like Particles Leads to Expansion of Specific Human T Cells

Leclerc

Beauseigle

Denis

et al. 2007

J Virol

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The development of versatile vaccine platforms is a priority that is recognized by health authorities worldwide; such platforms should induce both arms of the immune system, the humoral and cytotoxic-Tlymphocyte responses. In this study, we have established that a vaccine platform based on the coat protein of papaya mosaic virus (PapMV CP), previously shown to induce a humoral response, can induce major histocompatibility complex (MHC) class I cross-presentation of HLA-A*0201 epitopes from gp100, a melanoma antigen, and from influenza virus M1 matrix protein. PapMV proteins were able to assemble into stable virus-like particles (VLPs) in a crystalline and repetitive structure. When we pulsed HLA-A*0201؉ antigenpresenting cells (APCs) with the recombinant PapMV FLU or gp100, we noted that antigen-specific CD8 ؉ T cells were highly reactive to these APCs, demonstrating that the epitope from the VLPs were processed and loaded on the MHC class I complex. APCs were preincubated with two different proteasome inhibitors, which did not affect the efficiency of peptide presentation on MHC class I. Classical presentation from an endogenous antigen was abolished in the same conditions. Clearly, antigen presentation mediated by the PapMV system was proteasome independent. Finally, PapMV-pulsed APCs had the capacity to expand highly avid antigenspecific T cells against the influenza virus M1 HLA-A*0201 epitope when cocultured with autologous peripheral blood mononuclear cells. This study demonstrates the potential of PapMV for MHC class I crosspresentation and for the expansion of human antigen-specific T cells. It makes VLPs from PapMV CP a very attractive platform to trigger cellular responses for vaccine development against chronic infectious diseases and cancers.

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confidence: 99%

Proteasome-Independent Major Histocompatibility Complex Class I Cross-Presentation Mediated by Papaya Mosaic Virus-Like Particles Leads to Expansion of Specific Human T Cells

Leclerc

Beauseigle

Denis

et al. 2007

J Virol

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“…MF-59 has been tested with several different antigens in baboons, and there was a wide range of antibody titer augmentation over those elicited by the same antigen with alum: five to seven-fold for HSV gD2, Hib and MenC, but twenty-six-fold for HIV gp120 and forty-two-fold for HBsAg. 22 Results were somewhat less variable with CPG 7909 together with alum and several different antigens in healthy human volunteers (Table 2), but still not consistent enough to have strong predictive value.…”

Section: Specific Factors To Consider For Translating Pre-clinical Rementioning

confidence: 96%

Novel vaccines and adjuvant systems: The utility of animal models for predicting immunogenicity in humans

Davis¹

2008

Human Vaccines

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as for the prevention or treatment of cancer, allergy and autoimmune disorders, lifestyle related conditions (e.g., hypertension, smoking, contraception) and miscellaneous pathological states (e.g., Alzheimer's dementia). All vaccines contain one or more antigens, that can take various forms from peptides up to whole cells, and today many vaccines also contain an adjuvant. Such adjuvants are designed to affect the biodistribution of the antigen (e.g., provide a depot effect or target the antigen to particular immune cells) and/ or enhance resulting immune responses through direct activation of specific immune cells.Antigen discovery is not a new science, and for a long time there have been plenty of novel antigen candidates that were not being developed for want of an adjuvant system more potent than alum, which was, until fairly recently, the only adjuvant in a licensed vaccine. Alum is a relatively weak adjuvant with a strong Th2 bias, hence effective mostly for induction of antibodies. Thus, the need for novel adjuvants was particularly urgent for vaccines being designed for therapeutic applications where cell-mediated immunity is required for efficacy.Development of new vaccine adjuvants has been facilitated by two interrelated factors: (1) the rapidly expanding knowledge of the immune system, in particular the mechanisms by which the immune system naturally recognizes and responds to pathogens and how this innate immune activation is translated into adaptive immunity with memory, and (2) the discovery of natural or synthetic agonists for receptors that detect pathogen-associated molecular patterns and their development as potent new generation vaccine adjuvants.Successful development of a new vaccine formulation requires that the antigen and adjuvant components in the formulation are compatible, chemically distinct and detectable for quality control purposes. As well, they need to be sufficiently stable, have scalable and cost-effective synthesis, and last but certainly not least, be effective in inducing an adequate and appropriate immune response. The risk for most of these elements can be ascertained fairly quickly, but efficacy is a huge challenge. Certainly no one would consider testing a novel vaccine in humans without having achieved encouraging immunogenicity data in animals, but how useful or meaningful is the animal data for designing human studies and predicting outcome? There is a fair degree of judgment and guesswork required, and failure to do this well can lead to protracted and costly drug development pathways. Even with ultimate testing in human clinical trials, it may not be possible to measure efficacy directly when the pathogen is rarely Animal models are essential for acquiring safety, immunogenicity and efficacy data to support the development of novel vaccines. However, extrapolating such results to designing human trials is challenging due to species-specific differences in responses to antigens, adjuvants and pathogens. As well, most early vaccine work is conducted with in-bred mous...

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“…In conclusion, we show that mice can be protected against the novel H7N9 virus using a stalk-based immunization regimen with cHA constructs that do not possess an H7 head domain. Furthermore, an oil-in-water-based adjuvant similar to those licensed for use in humans (17,21) performed well with the cHA vaccine candidates, suggesting that this combination could also be considered for testing in humans. An HA stalk-based vaccine providing universal influenza virus protection could replace strain-specific seasonal vaccines and further enhance our preparedness against potential pandemic influenza virus strains like H7N9.…”

mentioning

confidence: 92%

“…Furthermore, to study the importance of mucosal responses for protection, we applied an experimental setup that induces both mucosal and systemic immunity and compared it to one that would induce only systemic immunity. We also compared two adjuvants, poly(I·C) (PIC), which we successfully used in combination with cHAs in animals before, and a generic oil-in-water (OIW) adjuvant (17). The latter is similar to adjuvants that have been licensed for use in humans (17).…”

mentioning

confidence: 99%

“…We also compared two adjuvants, poly(I·C) (PIC), which we successfully used in combination with cHAs in animals before, and a generic oil-in-water (OIW) adjuvant (17). The latter is similar to adjuvants that have been licensed for use in humans (17). Animals (n ϭ 10 per group, female 6-to 8-week-old BALB/c mice) were primed with a DNA plasmid expressing a cH4/3 protein (H4 head derived from A/duck/Czech/56 on top of an H3 stalk domain derived from A/Perth/16/09) (16) via intramuscular (i.m.)…”

mentioning

confidence: 99%

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H3 Stalk-Based Chimeric Hemagglutinin Influenza Virus Constructs Protect Mice from H7N9 Challenge

Krammer

Margine

Hai

et al. 2014

J Virol

106

109

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The recent outbreak of H7N9 influenza virus infections in humans in China has raised concerns about the pandemic potential of this strain. Here, we test the efficacy of H3 stalk-based chimeric hemagglutinin universal influenza virus vaccine constructs to protect against H7N9 challenge in mice. Chimeric hemagglutinin constructs protected from viral challenge in the context of different administration routes as well as with a generic oil-in-water adjuvant similar to formulations licensed for use in humans.

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The Adjuvant MF59: A 10-Year Perspective

Cited by 48 publications

References 18 publications

Proteasome-Independent Major Histocompatibility Complex Class I Cross-Presentation Mediated by Papaya Mosaic Virus-Like Particles Leads to Expansion of Specific Human T Cells

Proteasome-Independent Major Histocompatibility Complex Class I Cross-Presentation Mediated by Papaya Mosaic Virus-Like Particles Leads to Expansion of Specific Human T Cells

Novel vaccines and adjuvant systems: The utility of animal models for predicting immunogenicity in humans

H3 Stalk-Based Chimeric Hemagglutinin Influenza Virus Constructs Protect Mice from H7N9 Challenge

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