Vaccine composition containing synthetic adjuvant

Abstract

Compositions and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed based on the discovery of useful immunological adjuvant properties in a synthetic, glucopyranosyl lipid adjuvant (GLA) that is provided in substantially homogeneous form. Chemically defined, synthetic GLA offers a consistent vaccine component from lot to lot without the fluctuations in contaminants or activity that compromise natural-product adjuvants. Also provided are vaccines and pharmaceutical compositions that include GLA and one or more of an antigen, a Toll-like receptor (TLR) agonist, a co-adjuvant and a carrier such as a pharmaceutical carrier.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application is a continuation of U.S. patent application Ser. No. 12 / 134,127 filed Jun. 5, 2008, now pending; and a continuation-in-part of U.S. application Ser. No. 12 / 154,663, filed May 22, 2008, now pending; and a continuation-in-part of U.S. application Ser. No. 11 / 862,122 filed Sep. 26, 2007, now pending, which claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 60 / 847,404 filed Sep. 26, 2006; all of these applications are incorporated herein by reference in their entireties.STATEMENT OF GOVERNMENT INTEREST[0002]This invention was made in part with government support under Grant No. AI-25038 awarded by the National Institutes of Health. The government has certain rights in this invention.BACKGROUND OF THE INVENTION[0003]1. Field of the Invention[0004]The present invention relates to the field of pharmaceutical and vaccine compositions. More specifically, embodiments described herein relate to ph...

AI Technical Summary

Benefits of technology

[0073]FIG. 9 shows the surface expression of CD86 upon stimulation with GLA. Donor N003 CD14+ monocytes-derived primary dendritic cells were incubated for 44 hours with 10,000 ng / ml, 1000 ng / ml, 100 ng / ml, 10 ng / ml, 1 ng / ml, 0.1 ng / ml, or 0.01 ng / ml GLA (panel A) or MPL (panel B). A cytokine cocktail made of PGE2, IL-1β, TNFα, and IL-6 was run as a positive control. Expression levels of the costimulatory molecule CD86 at the surface of DC were used as an indicator of cell activation and measured by flow cytometry on a LSRII instrument (BD Biosciences, San Jose, Calif.) using CD86-specific fluorochrome -labeled antibody (eBiosciences, San Diego, Calif.).

[0074]FIG. 10 shows cultured human dendritic cells (DC) from three donors that show increased maturation with GLA stimulation. PBMC from three normal donors was purified for human CD14+ monocytes-derived primary dendritic cells and stimulated with GLA (panels A-C) or MPL (panels D-F). No stimulation was used as a negative control and a standard cytokine maturation cocktail of PGE2, IL-1β, TNFα, and IL-6 was run as a positive control. The percent maximum expression of CD86-specific fluorochrome-labeled antibody (eBiosciences, San Diego, Calif.) was used to monitor DC maturation by flow cytometry on a LSRII instrument (BD Biosciences, San Jose, Calif.)

Problems solved by technology

It has long been known that enterobacterial lipopolysaccharide (LPS) is a potent stimulator of the immune system, although its use in adjuvants has been curtailed by its toxic effects.

Despite the accessibility of such combinations, the use of adjuvants derived from natural products is accompanied by high production costs, inconsistency from lot to lot, difficulties associated with large-scale production, and uncertainty with respect to the presence of impurities in the compositional make-up of any given preparation.

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