Formulations of dengue virus vaccine compositions
The present invention relates to formulations of dengue virus vaccine comprising at least one live, attenuated dengue virus or live, attenuated chimeric flavivirus, a buffer, a sugar, a cellulose derivative, a glycol or sugar alcohol, optionally an alkali or alkaline salt and an amino acid; and formulations of dengue virus vaccine comprising at least one live, attenuated dengue virus or live, attenuated chimeric flavivirus, a buffer, a sugar of at least 150 mg/ml, a carrier, and optionally an alkali or alkaline salt and an amino acid.
1. A formulation comprising:
a) a live attenuated tetravalent dengue vaccine comprising i) 100-10,000,000 pfu/ml rDEN1430 virus, ii) 100-10,000,000 pfu/ml rDEN2/4430 virus, iii) 100-10,000,000 pfu/ml rDEN3Δ30/31 virus, and iv) 100-10,000,000 pfu/ml rDEN4Δ30 virus,
b) 5-300 mM potassium phosphate buffer at pH 7.0 to 8.0,
c) 60-120 mg/ml sucrose or trehalose or a combination thereof,
d) 3-7 mg/ml propylene glycol or glycerol, and
e) 3-7 mg/ml carboxymethylcellulose,
f) optionally 30-90 mM NaCl, and
g) optionally 10-75 mM amino acid Leu, Lys or Glu, or a combination thereof.
2. The formulation of claim 1 further comprising an aluminum adjuvant.
3. The formulation of claim 1 that is frozen or lyophilized.
4. The formulation of claim 1 that is reconstituted in solution.
5. The formulation of claim 1 that is in an aqueous solution prior to lyophilization or microwave vacuum drying.