Mutant enterotoxin effective as a non-toxic oral adjuvant
AssigneeThe Administrators of the Tulane Educational Fund
InventorsJohn D. Clements, Bonny L. Dickinson
Life of this patent
Estimating the term…
Abstract
Methods and compositions are provided herein for the se of a novel mutant form of E. coli heat-labile enterotoxin which has lost its toxicity but has retained its immunologic activity. This enterotoxin is used in combination with an unrelated antigen to achieve an increased immune response to said antigen when administered as part of an oral vaccine preparation.
Claims8
A vaccine preparation comprising an antigen in combination with a composition comprising a mutant E. coli heat-labile enterotoxin holotoxin, in which arginine at amino acid position 192 is replaced with glycine, which holotoxin is substantially less toxic than native E. coli heat-labile enterotoxin holotoxin as measured in the Y-1 adrenal cell assay and which has immunologic adjuvant activity but lacks ADP-ribosylating enzymatic activity as measured by the NAD-Agmatine ADP-ribosyltransferase assay.
A composition comprising (a) a vaccine selected from the group consisting of influenza vaccine, pertussis vaccine, diphtheria and tetanus toxoid combined with pertussis vaccine, hepatitis A vaccine, hepatitis B vaccine, hepatitis C vaccine, hepatitis E vaccine, Japanese encephalitis vaccine, herpes vaccine, measles vaccine, rubella vaccine, mumps vaccine, mixed vaccine of measles, mumps and rubella, papillomavirus vaccine, parvovirus vaccine, respiratory syncytial virus vaccine, Lyme disease vaccine, polio vaccine, malaria vaccine, varicella vaccine, gonorrhea vaccine, schistosomiasis vaccine, rota vaccine, Campylobacter vaccine, cholera vaccine, enteropathogenic E. coli vaccine, enterotoxic E. coli vaccine, mycoplasma vaccine, pneumococcal vaccine, and meningococcal vaccine, and (b) a composition comprising a mutant E. coli heat-labile enterotoxin holotoxin, in which arginine at amino acid position 192 is replaced with glycine, which holotoxin is substantially less toxic than native E. coli heat-labile enterotoxin holotoxin as measured in the Y-1 adrenal cell assay and which has immunologic adjuvant activity but lacks ADP-ribosylating enzymatic activity as measured by the NAD-Agmatine ADP-ribosyltransferase assay.
A kit useful in producing a protective immune response in a host to a pathogen comprising two components:
- (a) an effective amount of a protective antigen of a bacterial, viral or fungal pathogen, and (b) an adjuvant effective amount of a mutant E. coli heat-labile enterotoxin holotoxin, in which arginine at amino acid position 192 is replaced with glycine, and which has immunologic adjuvant activity but lacks ADP-ribosylating enzymatic activity as measured by the NAD-Agmatine ADP-ribosyltransferase assay, wherein both said components are in an orally acceptable carrier and said components may be administered either after having been mixed together or separately.
Dependencies are inferred from the claim text.