Vaccine compositions having improved stability and immunogenicity
Disclosed herein are nanoparticles suitable for use in vaccines. The nanoparticles present antigens from pathogens surrounded to and associated with a detergent core resulting in enhanced stability and good immunogenicity. Dosages, formulations, and methods for preparing the vaccines and nanoparticles are also disclosed.
1. A vaccine composition comprising:
(i) a nanoparticle comprising a non-ionic detergent core and a viral glycoprotein,
wherein the viral glycoprotein is associated with the core; wherein the non-ionic detergent is PS80 wherein the viral glycoprotein is an RSV F glycoprotein and the molar ratio of PS80 to viral glycoprotein is about 30:1 to about 60:1; and
(ii) a pharmaceutically acceptable buffer.
2. The vaccine composition of claim 1 , wherein the RSV F glycoprotein comprises a deletion of 1 to 10 amino acids corresponding to amino acids 137-146 of SEQ ID NO:2 and an inactivated primary furin cleavage site corresponding to amino acids 131 to 136 of SEQ ID NO:2, wherein the primary furin cleavage site is inactivated by mutation.
3. The vaccine composition of claim 2 , wherein the composition is substantially free of any other detergent.
4. The vaccine composition of claim 2 , wherein the RSV-F glycoprotein is selected from the group consisting of SEQ ID NOS:1-13 and variants of SEQ ID NOS:1-13 lacking part or all of the N-terminal signal peptide.
5. The vaccine composition of claim 4 , wherein the RSV F glycoprotein comprises SEQ ID NO:19.
6. The vaccine composition of claim 4 , wherein the RSV F glycoprotein consists of SEQ ID NO:19.
7. The vaccine composition of claim 1 , wherein the molar ratio is about 50:1.
8. The vaccine composition of claim 1 , wherein the pharmaceutically acceptable buffer comprises
(i) sodium phosphate at 15 mM to 25 mM;
(ii) NaCl at about 150 mM;
(iii) histidine at 0.25% to 2% w/v;
wherein the composition pH is between 5.8 and 6.4.
9. The vaccine composition of claim 8 , wherein the pharmaceutically acceptable buffer comprises
(i) sodium phosphate at about 22 mM;
(ii) NaCl at about 150 mM;
(iii) histidine at about 1%;
wherein the composition pH is about 6.2.
10. The vaccine composition of claim 1 , wherein the RSV F glycoprotein further comprises fatty acids linked to the protein.
11. The vaccine composition of claim 1 , wherein the nanoparticles have a Z-ave diameter of about 20 nm to about 60 nm.
12. The vaccine composition of claim 1 , wherein the shape of the nanoparticle is a spherical oligomer or an anisotropic rod.
13. The vaccine composition of claim 1 , wherein the vaccine composition is substantially free of any other detergent as determined by analytical ultracentrifugation.
14. The vaccine composition of claim 7 , wherein each nanoparticle comprises between 4 and 7 RSV F glycoprotein trimers.