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 that comprises the following components:
a) a live attenuated tetravalent dengue vaccine comprising i) about 100-10,000,000 pfu/ml rDEN1Δ30 virus, ii) about 100-10,000,000 pfu/ml rDEN2/4Δ30 virus, iii) about 100-10,000,000 pfu/ml rDEN3Δ30/31 virus, and iv) about 100-10,000,000 pfu/ml rDEN4Δ30 virus,
b) about 11 mM potassium phosphate buffer at a pH of about 7.0-8.0,
c) about 90 mg/ml sucrose,
d) about 5 mg/ml propylene glycol,
e) about 5 mg/ml sodium carboxymethylcellulose,
f) about 50 mM NaCl, and
g) about 25 mM Leu.
2. The formulation of claim 1 wherein the potassium phosphate buffer is at a pH of about 7.5.
3. The formulation of claim 1 wherein the vaccine comprises i) about 200-200,000 pfu/ml rDEN1Δ30 virus, ii) about 200-200,000 pfu/ml rDEN2/4Δ30 virus, iii) about 200-200,000 pfu/ml rDEN3Δ30/31 virus, and iv) about 200-200,000 pfu/ml rDEN4Δ30 virus.
4. The formulation of claim 1 wherein the rDEN1Δ30 is rDEN1Δ30-1545; the rDEN2/4Δ30 is rDEN2/4Δ30 (ME)-1495,7163; the rDEN3Δ30/31 is rDEN3430/31-7164; and the rDEN4Δ30 is rDEN4430-7132,7163,8308.
5. A formulation that comprises the following components:
a) a live attenuated tetravalent dengue vaccine comprising i) 100-10,000,000 pfu/ml rDEN1Δ30 virus, ii) 100-10,000,000 pfu/ml rDEN2/4Δ30 virus, iii) 100-10,000,000 pfu/ml rDEN3Δ30/31 virus, and iv) 100-10,000,000 pfu/ml rDEN4Δ30 virus,
b) 11 mM potassium phosphate buffer at a pH of 7.0-8.0,
c) 90 mg/ml sucrose,
d) 5 mg/ml propylene glycol,
e) 5 mg/ml sodium carboxymethylcellulose,
f) 50 mM NaCl, and
g) 25 mM Leu.
6. The formulation of claim 5 wherein the potassium phosphate buffer is at a pH of 7.5.
7. The formulation of claim 5 wherein the vaccine comprises i) 200-200,000 pfu/ml rDEN1Δ30 virus, ii) 200-200,000 pfu/ml rDEN2/4Δ30 virus, iii) 200-200,000 pfu/ml rDEN3Δ30/31 virus, and iv) 200-200,000 pfu/ml rDEN4Δ30 virus.
8. The formulation of claim 5 wherein the rDEN1Δ30 is rDEN1Δ30-1545; the rDEN2/4Δ30 is rDEN2/4Δ30 (ME)-1495,7163; the rDEN3Δ30/31 is rDEN3Δ30/31-7164; and the rDEN4Δ30 is rDEN4Δ30-7132,7163,8308.