Alphavirus and Alphavirus Replicon Particle Formulations and Methods

Abstract

Disclosed are methods for preparing dried (preferably lyophilized) preparations comprising a population of alphaviruses or alphavirus replicon particles, a sugar or polyol, a surfactant and a salt and preparations made by said methods, both in the dried form but also as liquids prior to drying or after reconstituting dried preparations. These preparations may further comprise a plasticizer and/or a bulking agent. These preparations are readily reconstituted, with little or no loss in infectivity of the viruses or replicon particles.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of U.S. Provisional Application 60 / 864,366, filed Nov. 3, 2006, which application is incorporated by reference to the extent there is no inconsistency with the present disclosure.REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING COMPACT DISK APPENDIX[0002]The sequence listing file herewith is incorporated by reference herein.BACKGROUND OF THE INVENTION[0003]A major impediment to worldwide vaccination efforts is the thermal lability of vaccines. Most vaccines are currently stored at temperatures below ambient through the maintenance of a “cold chain” from the manufacturing site to the administration site. While improvements in cold chain maintenance have been made, this system is expensive, remains error prone, and it does not always deliver potent vaccines to all parts of the world (Zaffran, 1996; Arya, 2001; Rexroad et al., 2002; Brandau et al., 2003). The vaccine stability problem is m...

AI Technical Summary

Benefits of technology

[0009]The present invention further encompasses methods for preparing alphavirus or alphavirus replicon particle preparations comprising the steps of (a) preparing an aqueous solution or dispersion comprising an alphavirus or alphavirus replicon particle, a salt, a surfactant, and a hydrogen-bonding sugar, sugar alcohol, or polyol; and optionally a plasticizer and / or a bulking agent; and (b) drying the aqueous dispersion to obtain a composition wherein the alphavirus or alphavirus replicon particle is dispersed in an amorphous glassy matrix containing the surfactant and sugar, sugar alcohol, or polyol, and optionally the plasticizer and / or bulking agent. It is preferred that the solution or dispersion of the virus or particles prior to drying is at a pH from about 7 to about 9 so as to prevent virus or particle breakdown.

Problems solved by technology

A major impediment to worldwide vaccination efforts is the thermal lability of vaccines.

While improvements in cold chain maintenance have been made, this system is expensive, remains error prone, and it does not always deliver potent vaccines to all parts of the world (Zaffran, 1996; Arya, 2001; Rexroad et al., 2002; Brandau et al., 2003).

The vaccine stability problem is made more difficult by the complexity of certain vaccine antigens such as attenuated viruses or bacteria.

These macromolecules are assemblies of various components (e.g., nucleic acids, proteins, lipids), and degradation in any of these components may adversely affect the potency of the entire vaccine.

However, for some virus pathogens, immunization with a live virus strain may be either impractical or unsafe.

In certain past studies, ARP formulations appeared to be relatively labile in solution, which has presented a hurdle in their commercial development.

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