Avirulent anti-rabies vaccine
AssigneeVirbac
InventorsJacqueline Benejean, Anne Flamand, Marie-Christine Tuffereau, Patrice Coulon, Florence Lafay
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Abstract
The invention relates to an avirulent anti-rabies vaccine which consists of an avirulent mutant of an SAD strain of the rabies virus, the glycoprotein of which possesses in position 333 a naturally occurring amino acid whose codon differs from those of arginine by at least two nucleotides.
Claims7
An isolated double avirulent mutant of the SAD Berne strain of rabies virus, deposited in the Collection Nationale de Cultures de Micro-organismes (C.N.C.M.)-INSTITUT PASTEUR-FRANCE on 9th Jul. 1992 under no. I-1238, said mutant having in position 333 glutamic acid, whose codon differs from all codons of arginine by at least two nucleotides.
An isolated avirulent anti-rabies vaccine which consists of an avirulent double base mutant of a SAD strain of the rabies virus, the glycoprotein of which possesses in position 333 a naturally occurring amino acid whose codon differs from all codons of arginine by at least two nucleotides;
- wherein said avirulent double base mutant is obtained from the process comprising the steps of:
- a) contacting a SAD strain of rabies virus with a first monoclonal antibody which neutralizes said SAD strain but does not neutralize the TAG1 strain of rabies virus, which TAG1 strain is deposited under n.degree.-I-433 in Collection Nationale de Cultures de Microorganismes;
- b) selecting from said SAD strain of rabies virus, those mutants not neutralized by said first monoclonal antibody;
- c) nucleotide-sequencing amino acid position 333 of the glycoprotein of said SAD mutants selected in step b;
- d) isolating, from said SAD mutants, nucleotide-sequenced in step c, those SAD mutants which possess a lysine in position 333;
- e) preparing a second monoclonal antibody which neutralizes both the said SAD strain and mutants isolated in step d, but does not neutralize the said TAG1 strain;
- and
- f) selecting from said SAD mutants selected in step b, those mutants which are not neutralized by said second monoclonal antibody.
A method of obtaining an isolated double base mutant avirulent anti-rabies vaccine possessing in position 333 an amino acid whose codon differs from all codons of arginine by at least two nucleotides, which comprises the steps of:
- a) contacting a SAD strain of rabies virus with a first monoclonal antibody which neutralizes said SAD strain but does not neutralize the TAG1 strain of rabies virus, which TAG1 strain is deposited under n.degree.-I-433 in Collection Nationale de Cultures de Microorganismes;
- b) selecting from said SAD strain of rabies virus, those mutants not neutralized by said first monoclonal antibody;
- c) nucleotide-sequencing amino acid position 333 of the glycoprotein of said SAD mutants selected in step b;
- d) isolating, from said SAD mutants nucleotide-sequenced in step c, those SAD mutants which possess a lysine in position 333;
- e) preparing a second monoclonal antibody which neutralizes both the SAD strain and SAD mutants isolated in step d, but does not neutralize the said TAG1 strain;
- and
- f) selecting from said SAD mutants selected in step b, those mutants which are not neutralized by said second monoclonal antibody.
Dependencies are inferred from the claim text.