Safety Evaluation of Monophosphoryl Lipid A (MPL): An Immunostimulatory Adjuvant

Baldrick, Paul; Richardson, Derek; Elliott, Gary T.; Wheeler, A. W.

doi:10.1006/rtph.2002.1541

Cited by 85 publications

(64 citation statements)

References 37 publications

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“…(MPL) is a detoxified lipopolysaccharide analog isolated from Salmonella enterica serovar Minnesota R595. The structure, mechanism of action, and immunologic responses to MPL have been the subjects of intense investigation for many decades (11), and the safety of MPL has been extensively documented (5,65). MPL has been successfully utilized as an adjuvant in numerous human vaccines, including vaccines for human papillomavirus 16/18 (HPV) (27,28,46), hepatitis B virus (HBV) (36,61), and herpes simplex virus (HSV) (57).…”

Section: Discussionmentioning

confidence: 99%

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

et al. 2010

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Haemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified from H. ducreyi class I strain 35000HP (nHgbA I ) and administered with Freund's adjuvant provided complete protection against a homologous challenge. In the current study, we investigated whether nHgbA I dispensed with monophosphoryl lipid A (MPL), an adjuvant approved for use in humans, offered protection against a challenge with H. ducreyi strain 35000HP expressing either class I or class II HgbA (35000HPhgbA I and 35000HPhgbA II , respectively). Pigs immunized with the nHgbA I /MPL vaccine were protected against a challenge from homologous H. ducreyi strain 35000HPhgbA I but not heterologous strain 35000HPhgbA II , as evidenced by the isolation of only strain 35000HPhgbA II from nHgbA I -immunized pigs. Furthermore, histological analysis of the lesions showed striking differences between mock-immunized and nHgbA I -immunized animals challenged with strains 35000HPhgbA I but not those challenged with strain 35000HPhgbA II . Mock-immunized pigs were not protected from a challenge by either strain. The enzyme-linked immunosorbent assay (ELISA) activity of the nHgbA I /MPL antiserum was lower than the activity of antiserum from animals immunized with the nHgbA I /Freund's vaccine; however, anti-nHgbA I from both studies bound whole cells of 35000HPhgbA I better than 35000HPhgbA II and partially blocked hemoglobin binding to nHgbA I . In conclusion, despite eliciting lower antibody ELISA activity than the nHgbA I /Freund's, the nHgbA I /MPL vaccine provided protection against a challenge with homologous but not heterologous H. ducreyi, suggesting that a bivalent HgbA vaccine may be needed.

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Section: Discussionmentioning

confidence: 99%

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

et al. 2010

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“…The distinction between AS01B and AS02A formulations resides in their liposome or oilin-water emulsion properties, respectively. Both adjuvants as well as their components are currently under clinical evaluation for various vaccines and has been tested in thousands of patients in several clinical trials, including infectious disease vaccines such as malaria (31,33), hepatitis B (50, 51), and allergy desensitization (52)(53)(54). Furthermore, the use of MPL-stable emulsion as an alternate adjuvant to IL-12, known for its Th1-inducing properties, in conjunction with a polyprotein Ag was recently demonstrated as a safe and effective vaccine against Leishmania infection (55).…”

Section: Discussionmentioning

confidence: 99%

Differential Immune Responses and Protective Efficacy Induced by Components of a Tuberculosis Polyprotein Vaccine, Mtb72F, Delivered as Naked DNA or Recombinant Protein

Skeiky

Alderson

Ovendale

et al. 2004

The Journal of Immunology

271

184

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Key Ags of Mycobacterium tuberculosis initially identified in the context of host responses in healthy purified protein derivative-positive donors and infected C57BL/6 mice were prioritized for the development of a subunit vaccine against tuberculosis. Our lead construct, Mtb72F, codes for a 72-kDa polyprotein genetically linked in tandem in the linear order Mtb32C-Mtb39-Mtb32N. Immunization of C57BL/6 mice with Mtb72F DNA resulted in the generation of IFN-γ responses directed against the first two components of the polyprotein and a strong CD8+ T cell response directed exclusively against Mtb32C. In contrast, immunization of mice with Mtb72F protein formulated in the adjuvant AS02A resulted in the elicitation of a moderate IFN-γ response and a weak CD8+ T cell response to Mtb32c. However, immunization with a formulation of Mtb72F protein in AS01B adjuvant generated a comprehensive and robust immune response, resulting in the elicitation of strong IFN-γ and Ab responses encompassing all three components of the polyprotein vaccine and a strong CD8+ response directed against the same Mtb32C epitope identified by DNA immunization. All three forms of Mtb72F immunization resulted in the protection of C57BL/6 mice against aerosol challenge with a virulent strain of M. tuberculosis. Most importantly, immunization of guinea pigs with Mtb72F, delivered either as DNA or as a rAg-based vaccine, resulted in prolonged survival (>1 year) after aerosol challenge with virulent M. tuberculosis comparable to bacillus Calmette-Guérin immunization. Mtb72F in AS02A formulation is currently in phase I clinical trial, making it the first recombinant tuberculosis vaccine to be tested in humans.

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“…Red blood cells were removed by lysis with ACK buffer (150 mM NH 4 Cl, 10 mM KHCO 3 , 0.1 mM Na 2 EDTA), and the remaining cells were washed twice in PBS. For the antigen-specific proliferation or cytokine expression assays, splenocytes (2 ϫ 10 6 to 4 ϫ 10 6 /ml) were resuspended in RPMI 1640 medium supplemented with 2% FBS, 200 nM L-glutamine, and penicillin-streptomycin (100 U/ml and 100 g/ml).…”

Section: Methodsmentioning

confidence: 99%

Mucosal Immunization with a Novel Nanoemulsion-Based Recombinant Anthrax Protective Antigen Vaccine Protects againstBacillus anthracisSpore Challenge

et al. 2007

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The currently available commercial human anthrax vaccine requires multiple injections for efficacy and has side effects due to its alum adjuvant. These factors limit its utility when immunizing exposed populations in emergent situations. We evaluated a novel mucosal adjuvant that consists of a nontoxic, water-in-oil nanoemulsion (NE). This material does not contain a proinflammatory component but penetrates mucosal surfaces to load antigens into dendritic cells. Mice and guinea pigs were intranasally immunized with recombinant Bacillus anthracis protective antigen (rPA) mixed in NE as an adjuvant. rPA-NE immunization was effective in inducing both serum anti-PA immunoglobulin G (IgG) and bronchial anti-PA IgA and IgG antibodies after either one or two mucosal administrations. Serum anti-PA IgG2a and IgG2b antibodies and PA-specific cytokine induction after immunization indicate a Th1-polarized immune response. rPA-NE immunization also produced high titers of lethal-toxin-neutralizing serum antibodies in both mice and guinea pigs. Guinea pigs nasally immunized with rPA-NE vaccine were protected against an intradermal challenge with ϳ1,000 times the 50% lethal dose (ϳ1,000؋ LD 50 ) of B. anthracis Ames strain spores (1.38 ؋ 10 3 spores), which killed control animals within 96 h. Nasal immunization also resulted in 70% and 40% survival rates against intranasal challenge with 10؋ LD 50 and 100؋ LD 50 (1.2 ؋ 10 6 and 1.2 ؋ 10 7 ) Ames strain spores. Our results indicate that NE can effectively adjuvant rPA for intranasal immunization. This potentially could lead to a needle-free anthrax vaccine requiring fewer doses and having fewer side effects than the currently available human vaccine.

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Safety Evaluation of Monophosphoryl Lipid A (MPL): An Immunostimulatory Adjuvant

Cited by 85 publications

References 37 publications

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

Differential Immune Responses and Protective Efficacy Induced by Components of a Tuberculosis Polyprotein Vaccine, Mtb72F, Delivered as Naked DNA or Recombinant Protein

Mucosal Immunization with a Novel Nanoemulsion-Based Recombinant Anthrax Protective Antigen Vaccine Protects againstBacillus anthracisSpore Challenge

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