Human papillomavirus vaccine formulations

Details Human papillomavirus vaccine formulations Human papillomavirus vaccine formulations

2000-02-02

2001-06-26

Salimi, Ali R. (Department: 1648)

Chemistry: analytical and immunological testing

Composition for standardization, calibration, simulation,...

C436S018000, C424S204100, C530S350000, C530S300000

Reexamination Certificate

active

06251678

ABSTRACT:

FIELD OF THE INVENTION
This invention related to human papillomavirus (HPV) vaccine formulations which provide enhanced long-term storage stability.
BACKGROUND OF THE INVENTION
Human Papillomavirus (HPV) infects the genital tract and has been associated with various dysplasias, cancers, and other diseases. These diseases are currently targets for vaccine development and vaccines containing virus-like particles (VLPs) which contain L1 or the combination of L1+L2 proteins are currently in clinical trials.
It has been found, however, that HPV VLPs are not stable during long-term storage, either in solution or when absorbed onto aluminum adjuvant particles.
In order to develop a commercially useful vaccine, a stable formulation is needed.
BRIEF DESCRIPTION OF THE INVENTION
This invention relates to human papillomavirus (HPV) vaccine formulations which exhibit long-term stability, the vaccines comprising: a) HPV virus-like particles (VLPs) which are adsorbed on an aluminum adjuvant; b) a salt; c) a buffer which provides for a pH range of the vaccine solution of from about pH 6.0 to about 6.5; and d) a non-ionic surfactant. In another embodiment, the formulation further comprises a polymeric polyanionic stabilizer.
Another embodiment of this invention is a vaccine comprising: a) 10-200 mcg/ml of each HPV VLP type adsorbed onto aluminum; wherein the VLPs are selected from the group consisting of: HPV 6a, HPV 6b, HPV 11, HPV 16, HPV 18, and mixtures thereof; b) 0.15 M NaCl; c) 0.05% carboxymethyl cellulose; and d) optional buffer agents and/or nonionic detergents.
This invention also relates to an improved stable vaccine formulation made by (i) adjusting the ionic strength of the solution with varying concentrations of salts; adjusting and controlling the pH of the solution with particular buffering agents; (iii) adding an non-ionic surfactant; and (iv) adding additional stabilizing excipients in the form of polymeric polyanions.


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