Methods and compositions for intranasal delivery
Provided herein are methods for generating dry vaccine powder formulations. Dry vaccine powder formulations can be used for intranasal delivery. Also provided are methods for stimulating local mucosal and systemic immunity by intranasal vaccine delivery.
1. A method for generating an intranasal dry vaccine powder formulation, comprising:
(a) preparing a liquid formulation comprising one or more antigens and one or more saccharides;
(b) quick freezing the liquid formulation to form a freeze-dried sample having an average particle diameter size of 10 to 100 microns without using a mill, wherein the quick freezing does not comprise spray freezing, and wherein the freeze-dried sample does not comprise an adjuvant; and
(c) blending the freeze-dried sample with one or more excipients to generate the intranasal dry vaccine powder formulation.
2. The method of claim 1 , wherein at least one of the one or more antigens is a viral antigen.
3. The method of claim 1 , wherein at least one of the one or more antigens is influenza virus.
4. The method of claim 1 , wherein at least one of the one or more antigens is H1N1 influenza virus.
5. The method of claim 1 , wherein at least one of the one or more antigens is H5N1 influenza virus.
6. The method of claim 1 , wherein the one or more antigens comprises H1N1 influenza virus, H3N2 influenza virus, and Influenza B virus.
7. The method of claim 1 , wherein at least one of the one or more antigens is live attenuated virus, whole inactivated virus, split virus, subunit antigen, virosome, or cold-adapted live influenza virus.
8. The method of claim 1 , wherein at least one of the one or more antigens is a bacterial antigen.
9. The method of claim 1 , wherein at least one of the one or more antigens is killed whole bacteria, attenuated bacteria, toxoids, purified surface protein, or purified recombinant surface protein.
10. The method of claim 1 , wherein at least one of the one or more antigens is tetanus toxoid.
11. The method of claim 1 , wherein at least one of the one or more antigens is diphtheria toxoid.
12. The method of claim 1 , wherein at least one of the one or more antigens is a protist antigen.
13. The method of claim 1 , wherein at least one of the one or more antigens is a protein.
14. The method of claim 1 , wherein at least one of the one or more saccharides is lactose.
15. The method of claim 1 , wherein at least one of the one or more saccharides is trehalose.
16. The method of claim 1 , wherein at least one of the one or more saccharides is mannitol.
17. The method of claim 1 , wherein the liquid formulation further comprises one or more buffers.
18. The method of claim 17 , wherein at least one of the one or more buffers is a phosphate buffer.
19. The method of claim 1 , wherein the quick freezing comprises exposing the liquid formulation to a cold liquid for 1 minute to 60 minutes.
20. The method of claim 19 , wherein the cold liquid is liquid nitrogen.
21. The method of claim 1 , wherein the one or more excipients comprise tribasic calcium phosphate (TCP).
22. The method of claim 1 , wherein the intranasal dry vaccine powder formulation does not comprise an adjuvant.