Synthetic nanocarrier combination vaccines

Abstract

Disclosed are dosage forms and related methods, that include a first population of synthetic nanocarriers that have one or more first antigens coupled to them, one or more second antigens that are not coupled to the synthetic nanocarriers, and a pharmaceutically acceptable excipient.

Description

RELATED APPLICATIONS[0001]This application claims the benefit under 35 U.S.C. §119 of U.S. provisional applications 61 / 348,713, filed May 26, 2010, 61 / 348,717, filed May 26, 2010, 61 / 348,728, filed May 26, 2010, and 61 / 358,635, filed Jun. 25, 2010, the entire contents of each of which are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]To either minimize the number of childhood vaccinations and / or to provide broader immune protection against different strains of a given pathogen, there often is a desire to combine multiple antigens in a single dosage form, the resulting vaccine being termed a multivalent vaccine. The number of antigens that can be combined in a single dosage form may be limited by the amount of each antigen required to elicit the desired immune response and the aqueous solubility of the antigen.[0003]At some point, the total liquid volume of the dosage form becomes too large to comfortably and / or safely administer the vaccine by an intramuscular an...

AI Technical Summary

Benefits of technology

[0030]For example, the vaccines Gardasil® and Cervarix® for protection against HPV comprise protein antigen epitopes from the major structural protein L1 protein derived from 4 and 2 sets of HPV strains, correspondingly. Vaccines with L1 peptide antigens from as many as 9 different HPV strains are known. Such a vaccine with multiple peptide antigens would potentially protect the individual against most, but not all, HPV strains. If a population of synthetic nanocarriers comprising one or more peptide epitopes from another HPV structural protein, L2, is added to an existing L1 protein-based vaccine, broader protection from an HPV challenge would be obtained with the potential of creating a “universal HPV vaccine.” This population of water-dispersed L2 peptide synthetic nanocarriers can simply be admixed to the existing aqueous vaccine formulation much as one would add an excipient, or diluent, to the formulation. This simple method for expanding the breadth of coverage avoids having to engineer the L2 peptide into a recombinant protein antigen form as is conventionally done. This is illustrated in Examples 1 and 2 below, which together illustrate the formation of a combination HPV vaccine containing conventional Gardasil® augmented by synthetic nanocarriers comprising a peptide derived from L2 protein.

Problems solved by technology

The number of antigens that can be combined in a single dosage form may be limited by the amount of each antigen required to elicit the desired immune response and the aqueous solubility of the antigen.

At some point, the total liquid volume of the dosage form becomes too large to comfortably and / or safely administer the vaccine by an intramuscular and / or subcutaneous route.

Another limitation of existing vaccine formulations is their limited coverage or their physical incompatibility with one another which may preclude simple blending of two existing vaccines to create a new, combination vaccine.

These vaccines do not provide protection against all strains of HPV.

It certain circumstances it may not be possible to simply blend in additional conventionally produced antigens to an existing vaccine because of undesirable interactions between the additional conventionally produced antigens and the existing vaccine (which may lead to precipitation, aggregation, etc.).

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