Multivalent synthetic nanocarrier vaccines

Abstract

The invention relates, at least in part, to compositions comprising populations of synthetic nanocarriers that comprise different sets of antigens as well as related methods.

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]Multivalent vaccines are a useful way of generating an immune response to certain foreign substances that otherwise would not be desirably robust. For instance, vaccinating against multiple strains of a virus may provide more robust cross-protection against multiple strains of that virus as compared to vaccinating using a monovalent vaccine.[0003]However, current multivalent vaccines and methods of making them need improvement. For instance, current approaches of conjugating antigens to protein carriers are complex and provide for low yields. Additionally, new techniques often need to be developed to conjugate new antigens to carrier...

AI Technical Summary

Benefits of technology

[0067]A further advantage of the present invention is that combining different populations of synthetic nanocarriers that comprise sets of surface antigens allows different methods to be used to couple different sets of surface antigens to different populations of synthetic nanocarriers. This can be a significant advantage for embodiments wherein incompatible coupling methods are required to couple sets of surface antigens to populations of synthetic nanocarriers. As an example, vaccines for Streptococcus pneumonia (U.S. Pat. No. 6,132,723 to Alberta Research Council and WO 2008 / 143709 to Wyeth) contain multiple antigens. Since the attachment chemistry conditions are not the same for all of the polysaccharide antigens (WO 2008 / 143709) coupling methods that would attach all of the surface antigens to a single population of synthetic nanocariers in a single coupling environment would be undesirable. Practicing embodiments of the present invention wherein different populations of synthetic nanocarriers are first coupled to certain sets of surface antigens and then combined could ameliorate the problem noted in the art.

[0068]Another example of multivalent vaccines that could benefit from this embodiment of the invention comprise vaccines against N. meningitides which is polysaccharide-based and multivalent. Such embodiments may be aimed either at N. meningitidis groups A and C (bivalent) or groups A, C, W135 and Y (tetravalent).

[0069]The examples illustrate certain embodiments according to the invention, wherein peptides, polysaccharides, small molecules, etc., are conjugated to a first population of synthetic nanocarriers and / or a second population of synthetic nanocarriers. These populations are then combined to form a composition according to the invention.

[0070]The present invention will now be described in more detail.Definition

[0071]“Abused substance” is any substance taken by a subject (e.g., a human) for purposes other than those for which it is indicated or in a manner or in quantities other than directed by a physician. The abused substance, in some embodiments, is an addictive substance. In some embodiments, the abused substance for inclusion in a nanocarrier is the complete molecule, analog or a portion thereof. “Addictive substance” is a substance that causes obsession, compulsion, or physical dependence or psychological dependence. In some embodiments, the addictive substance for inclusion in a nanocarrier is the complete molecule, analog or a portion thereof.

[0072]“Adjuvant” means an agent that does not constitute a specific antigen, but boosts the strength and longevity of immune response to an administered antigen (e.g., a concomitantly administered antigen). Such adjuvants may include, but are not limited to stimulators of pattern recognition receptors, such as Toll-like receptors, RIG-1 and NOD-like receptors (NLR), mineral salts, such as alum, alum combined with monphosphoryl lipid (MPL) A of Enterobacteria, such as Escherichia coli, Salmonella minnesota, Salmonella typhimurium, or Shigella flexneri or specifically with MPL® (AS04), MPL A of above-mentioned bacteria separately, saponins, such as QS-21,Quil-A, ISCOMs, ISCOMATRIX™, emulsions such as MF59™, Montanide® ISA 51 and ISA 720, AS02 (QS21+squalene+MPL®) , liposomes and liposomal formulations such as AS01, AS15, synthesized or specifically prepared microparticles and microcarriers such as bacteria-derived outer membrane vesicles (OMV) of N. gonorrheae, Chlamydia trachomatis and others, or chitosan particles, depot-forming agents, such as Pluronic® block co-polymers, specifically modified or prepared peptides, such as muramyl dipeptide, aminoalkyl glucosaminide 4-phosphates, such as RC529, or proteins, such as bacterial toxoids or toxin fragments.

Problems solved by technology

However, current multivalent vaccines and methods of making them need improvement.

For instance, current approaches of conjugating antigens to protein carriers are complex and provide for low yields.

Additionally, new techniques often need to be developed to conjugate new antigens to carrier proteins because conventional techniques can be unsuccessful due to the relative fragility of conventional carrier proteins.

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