A Th1-inducing adjuvant, MPL, enhances antibody profiles in experimental animals suggesting it has the potential to improve the efficacy of allergy vaccines.
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.
Wheeler
A W
AW
Allergy Therapeutics Ltd, Worthing, UK. alan.wheeler@allergytherapeutics.com
Marshall
J S
JS
Ulrich
J T
JT
D000276:Adjuvants, Immunologic; D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D000906:Antibodies / Q000097:blood*; D052179:Antigens, Plant / Q000627:therapeutic use; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006969:Hypersensitivity, Immediate / Q000517:prevention & control; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010936:Plant Extracts / Q000276:immunology; D051381:Rats; D018417:Th1 Cells / Q000276:immunology*; D014443:Tyrosine / Q000737:chemistry / Q000276:immunology; D014612:Vaccines
D000276:Adjuvants, Immunologic; D000485:Allergens; D000906:Antibodies; D052179:Antigens, Plant; D007074:Immunoglobulin G; D008050:Lipid A; D010936:Plant Extracts; D014612:Vaccines; C433085:ragweed pollen; D007073:Immunoglobulin E; D014443:Tyrosine; D010047:Ovalbumin; C048436:monophosphoryl lipid A