Ability of monophosphoryl lipid A to augment the antibody response of young mice

Baker, Phillip J.; Hiernaux, Jean; Fauntleroy, Michael B.; Stashak, Philip W.; Prescott, Benjamin; Cantrell, John L.; Rudbach, Jon A.

doi:10.1128/iai.56.12.3064-3066.1988

Cited by 45 publications

(30 citation statements)

References 14 publications

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“…The magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III) is regulated in a negative and positive manner by the competitive interaction of thymus-derived CD8+ CD4suppressor T cells (Ts) and CD8-CD4+ amplifier T cells, respectively (reviewed in reference 2). Treatment with monophosphoryl lipid A (MPL) abolishes expression of Ts activity without adversely effecting expression of amplifier and helper T cell functions; this permits the positive effects of amplifier T cells on antigen-stimulated B cells to be more fully expressed, thereby resulting in either an increased antibody response to SSS-III or abrogation of Ts-mediated immunological unresponsiveness (6,7,13).…”

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confidence: 99%

“…The immunological properties of SSS-III and the method by which it was prepared have already been described (3,(8)(9)(10)(11). MPL from S. minnesota R595 was purchased from Ribi ImmunoChem Research, Inc., Hamilton, Mont., and reconstituted in 0.2% triethylamine as previously described (6,7,15). Data on the pharmacological and immunological properties of relatively nontoxic MPL, as well as the toxic parent LPS and diphosphoryl lipid A from which it was derived, have already been reported (18,19).…”

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confidence: 99%

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Differential effects of monophosphoryl lipid A on expression of suppressor T cell activity in lipopolysaccharide-responsive and lipopolysaccharide-defective strains of C3H mice

et al. 1991

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Lipopolysaccharide (LPS)-responsive and LPS-defective strains of C3H mice did not differ in the capacity to make an antibody response to type III pneumococcal polysaccharide or in the degree of thymus-derived suppressor cell (Ts) activity generated following exposure to type III pneumococcal polysaccharide. However, treatment with monophosphoryl lipid A (MPL) abolished the expression of Ts function in LPS-responsive but not LPS-defective mice. Since this effect was elicited by different preparations of MPL, it appears to be a general property of MPL mediated by direct action of MPL on activated Ts.

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confidence: 99%

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Differential effects of monophosphoryl lipid A on expression of suppressor T cell activity in lipopolysaccharide-responsive and lipopolysaccharide-defective strains of C3H mice

et al. 1991

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“…Alum allows extended antigen presentation and stimulates T-helper (Th)-2 responses, predominantly producing IgG1 and IgE (Marrack, McKee et al, 2009, Moingeon, Haensler et al, 2001, Petrovsky & Aguilar, 2004, while MPLA typically enhances Th1 responses, inducing IgG2a, IgG2b, and IgG3 (Baker, Hiernaux et al, 1988, Germann, Bongartz et al, 1995. Murine IgG2a has a greater ability than murine IgG1 to activate the classical pathway (Leatherbarrow & Dwek, 1984, Michaelsen, Kolberg et al, 2004.…”

Section: Discussionmentioning

confidence: 99%

Structural Design of Chimeric Antigens for Multivalent Protein Vaccines

Hollingshead

Jongerius

Exley

et al. 2017

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Running title: Structural design of multivalent vaccinesThe development of prophylactic vaccines against pathogenic bacteria is a major objective of the World Health Organisation. However, vaccine development is often hindered by antigenic diversity and the difficulties encountered manufacturing immunogenic membrane proteins. Here, we employed structure-based design as a strategy to develop Chimeric Antigens (ChAs) for subunit vaccines. ChAs were generated against serogroup B Neisseria meningitidis (MenB), the predominant cause of meningococcal disease in the Western hemisphere. MenB ChAs exploit the lipoprotein factor H binding protein (fHbp) as a molecular scaffold to display the immunogenic VR2 epitope from the integral membrane protein PorA. Structural analyses demonstrate fHbp is correctly folded and that PorA VR2 epitope adopts an immunogenic conformation. In mice, ChAs elicit antibodies directed against fHbp and PorA, with antibody responses correlating to protection against meningococcal disease. ChAs offer a novel approach for generating multivalent subunit vaccines, containing of epitopes from integral membrane proteins, whose composition can be selected to circumvent pathogen diversity.

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“…on August 5, 2020 by guest http://iai.asm.org/ Downloaded from [6] 5.290 ± 0.033 (194,964) [6] a TDM was given i.p. 2 days after i.p.…”

Section: Infect Immunmentioning

confidence: 99%

“…Although monophosphoryl lipid A (MPL) and cord factor or trehalose dimycolate (TDM) have been shown to augment the antibody response to several antigens (5,6,14,(27)(28)(29), the combination of MPL and TDM is an extremely potent immunological adjuvant (25,26). In some cases, the effect produced by administration of both MPL and TDM is synergistic rather than additive (25,26).…”

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Adjuvant effects of trehalose dimycolate on the antibody response to type III pneumococcal polysaccharide

et al. 1989

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Treatment with trehalose dimycolate (TDM) increases the magnitude of the immunoglobulin M (IgM) antibody response of mice to type III pneumococcal polysaccharide (SSS-III). Such enhancement is demonstrable over a wide range of immunizing doses and does not require thymus-derived (T) cells to be elicited. Although young adult mice immunized with SSS-III do not usually make anti-SSS-III antibodies of the IgGl and IgG3 classes, antibodies of one or both isotypes were produced after immunization and treatment with TDM and/or monophosphoryl lipid A (MPL); the additive nature of the effect produced by both TDM and MPL suggests that the two immunomodulators act by different mechanisms. TDM and MPL have different effects on the induction and expression of low-dose immunological paralysis, a form of unresponsiveness known to be mediated by suppressor T cells. The relevance of these findings to the modes of action of TDM and MPL is discussed.

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Ability of monophosphoryl lipid A to augment the antibody response of young mice

Cited by 45 publications

References 14 publications

Differential effects of monophosphoryl lipid A on expression of suppressor T cell activity in lipopolysaccharide-responsive and lipopolysaccharide-defective strains of C3H mice

Differential effects of monophosphoryl lipid A on expression of suppressor T cell activity in lipopolysaccharide-responsive and lipopolysaccharide-defective strains of C3H mice

Structural Design of Chimeric Antigens for Multivalent Protein Vaccines

Adjuvant effects of trehalose dimycolate on the antibody response to type III pneumococcal polysaccharide

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