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 method of stimulating an immune response in a subject comprising administering 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 method of claim 1 , wherein the vaccine composition is administered intramuscularly.
3. The method of claim 1 , wherein a single dose of the vaccine composition is administered.
4. The method of claim 1 , wherein multiple doses of the vaccine composition are administered.
5. The method of claim 1 , wherein a dose of the vaccine composition comprises between about 30 μg and about 150 μg of the RSV F glycoprotein.
6. The method of claim 1 , wherein the subject is selected from the group consisting of an adult, a senior adult, a pregnant female adult, a child, a neonate, and an infant.
7. The method of claim 1 , wherein the composition comprises an adjuvant.
8. The method of claim 7 , wherein the adjuvant comprises at least two iscom particles, wherein: the first iscom particle comprises fraction A of Quillaja Saponaria Molina and not fraction C of Quillaja Saponaria Molina; and the second iscom particle comprises fraction C of Quillaja Saponaria Molina and not fraction A of Quillaja Saponaria Molina.
9. The method of claim 8 , wherein the two iscom matrix particles are present in a composition of about 70% (w/w) of the first iscom particle and about 30% (w/w) of the second iscom particle.
10. The method of claim 8 , wherein the two iscom matrix particles are present in a composition of about 85% (w/w) of the first iscom particle and about 15% (w/w) of the second iscom particle.
11. The method of claim 7 , wherein the adjuvant comprises iscom matrix particles comprising a mixture of fraction A of Quillaja Saponaria Molina and fraction C of Quillaja Saponaria Molina.
12. The method of claim 11 , wherein the mixture comprises about 70% (w/w) of fraction A of Quillaja Saponaria Molina and about 30% (w/w) of fraction C of Quillaja Saponaria Molina.
13. The method of claim 11 , wherein the mixture comprises about 85% (w/w) of fraction A of Quillaja Saponaria Molina and about 15% (w/w) of fraction C of Quillaja Saponaria Molina.
14. The method of claim 7 , wherein the adjuvant is an alum adjuvant.
15. The method of claim 1 , wherein the composition contains no added adjuvant.
16. The method of claim 1 , wherein a dose of the vaccine composition is administered in a volume of about 0.5 mL.
17. The method of claim 1 , wherein a dose of the vaccine composition comprises about 87.5 μg to about 162.5 μg of an RSV F glycoprotein.
18. The method of claim 1 , wherein a dose of the vaccine composition comprises about 100 μg to about 300 μg of an RSV F glycoprotein.
19. The method of claim 1 , wherein a dose of the vaccine composition comprises about 120 μg to about 130 μg of an RSV F glycoprotein.
20. The method 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.
21. The method of claim 20 , wherein the RSV F glycoprotein is selected from the group consisting of SEQ ID NOS:3-12 and variants of SEQ ID NOS:3-12 lacking part or all of the N-terminal signal peptide.
22. The method of claim 21 , wherein the RSV F glycoprotein comprises SEQ ID NO:19.
23. The method of claim 21 , wherein the RSV F glycoprotein consists of SEQ ID NO:19.
24. The method of claim 1 , wherein the molar ratio is about 50:1.
25. The method of claim 1 , wherein the pharmaceutically acceptable buffer comprises
(i) sodium phosphate at about 15 mM to about 25 mM;
(ii) sodium chloride at about 150 mM;
(iii) histidine at 0.25% w/v to 2% w/v;
wherein the pH of the composition is between 5.8 and 6.4.
26. The method of claim 1 , wherein the pharmaceutically acceptable buffer comprises
(i) sodium phosphate at about 22 mM;
(ii) sodium chloride at about 150 mM;
(iii) histidine at about 1% w/v;
wherein the pH of the composition is about 6.2.
27. The method of claim 1 , wherein the RSV F glycoprotein comprises an RSV F1 and an RSV F2 domain connected by a disulfide bond.