Bacterial cell wall products as adjuvants: early interferon gamma as a marker for adjuvants that enhance protective immunity

Gustafson, Gary L.; Rhodes, Michael J.

doi:10.1016/0923-2494(92)80058-s

Cited by 50 publications

(23 citation statements)

References 26 publications

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“…The induction of high serum concentrations of interferonγ (IFNγ) in vivo by MPL ® in a mouse system has been reported [16]. Although not measured in this rat model, the induction of a rapid IFNγ response by MPL ® could serve to inhibit further activation of IgE-promoting Th2 cells by booster administrations of KLH.…”

Section: Resultsmentioning

confidence: 99%

A Th1-Inducing Adjuvant, MPL<sup>®</sup>, Enhances Antibody Profiles in Experimental Animals Suggesting It Has the Potential to Improve the Efficacy of Allergy Vaccines

Wheeler

Marshall

Ulrich

2001

Int Arch Allergy Immunol

103

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Background: Monophosphoryl lipid A (MPL^®) is a detoxified derivative of the lipopolysaccharide (LPS) moiety of Salmonella minnesota R595, which has retained immunostimulatory activities. MPL^® has been administered to many subjects in clinical trials as an adjuvant component of infectious disease vaccines and is currently a component of a licensed cancer vaccine, Melacine^® (Corixa Inc., Schering Plough). MPL^® has, in particular, been shown to promote Th1-type antigen specific responses. L-tyrosine is a depot adjuvant which is fully metabolisable and has been successfully employed in allergy vaccines for a number of years. Methods: Mice were immunised with MPL^® adjuvant in conjunction with separate preparations of either ovalbumin or glutaraldehyde-modified ragweed pollen extract both coprecipitated with L-tyrosine. The specific antibody isotypes IgG1, IgG2a, IgG2b and also IgE were measured. Rats received booster injections of keyhole limpet haemocyanin (KLH) in conjunction with MPL^® adjuvant following priming with KLH in alum alone. KLH-specific antibody responses were measured. Results: It was shown that a combination of L-tyrosine and MPL^® were synergistic in enhancing murine antigen specific IgG antibody responses without enhancing antigen specific IgE responses. Furthermore, this adjuvant combination promoted strong IgG2 antigen specific responses indicative of a Th1 directed response. In KLH sensitised rats, treatment with MPL^® was shown to prevent a secondary IgE antibody response when injected with booster injections of antigen. Conclusions: Immunisation of mice with two different antigens adsorbed to L-tyrosine induced a Th1-skewed primary response when in conjunction with MPL^® adjuvant which also generally enhances a specific IgG response. Incorporation of MPL^® adjuvant in the immunisation of rats prevented a secondary specific IgE response. These results suggest that the employment of this new adjuvant in clinical allergy vaccination formulations may result in an improved efficacy which could be utilised in various ways to improve compliance.

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Section: Resultsmentioning

confidence: 99%

A Th1-Inducing Adjuvant, MPL<sup>®</sup>, Enhances Antibody Profiles in Experimental Animals Suggesting It Has the Potential to Improve the Efficacy of Allergy Vaccines

Wheeler

Marshall

Ulrich

2001

Int Arch Allergy Immunol

103

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“…Early studies [29,30] showed that the adjuvant activity of RIBI reflects its ability to activate macrophages and stimulate IFN-γ and interleukin 2 (IL-2) [31] production, known to be essential for the induction of Th1-derived cell-mediated immunity. Moreover, inclusion of RIBI improved the transfection efficiency of pITR/CMV-LacZ and pCMV-LacZ into HEK 293 cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

A DNA vaccine containing inverted terminal repeats from adeno‐associated virus increases immunity to HIV

Xin

Ooki

Jounai

et al. 2002

The Journal of Gene Medicine

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“…Adjuvants generally function by stimulating the activity of APCs such that the associated protein is efficiently taken up and presented in an immunogenic fashion to T cells. As our understanding of immunity has improved, a variety of structures that naturally have adjuvant-like properties have been identified including certain toxins (Lyche 2005;Choi et al 2006), components of bacterial cell walls (Gustafson and Rhodes 1992;Jalava et al 2003), DNA with CpG motifs (Krieg 2002), double-stranded RNA (Cui and Xiu 2006), and uric acid crystals released by dying cells (Shi et al 2003). Strategies currently used to make antigens expressed by plants more immunogenic are, for the most part, based on those successful for other nonreplicating antigens, including the incorporation of an apathogenic toxin in the construct (Choe et al 2006).…”

Section: Enhancing Immunogenicity Of a Potential Plant Vaccine Versusmentioning

confidence: 99%

Plant Vaccines: An Immunological Perspective

Hooper

2009

Current Topics in Microbiology and Immunology

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Bacterial cell wall products as adjuvants: early interferon gamma as a marker for adjuvants that enhance protective immunity

Cited by 50 publications

References 26 publications

A Th1-Inducing Adjuvant, MPL<sup>®</sup>, Enhances Antibody Profiles in Experimental Animals Suggesting It Has the Potential to Improve the Efficacy of Allergy Vaccines

A Th1-Inducing Adjuvant, MPL<sup>®</sup>, Enhances Antibody Profiles in Experimental Animals Suggesting It Has the Potential to Improve the Efficacy of Allergy Vaccines

A DNA vaccine containing inverted terminal repeats from adeno‐associated virus increases immunity to HIV

Plant Vaccines: An Immunological Perspective

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