Mucosal Immunization

Abstract

Methods and compositions for eliciting an immune response to an antigen are disclosed. In certain aspects, these methods concern eliciting an immune response in a subject by administering to the mucosa of the subject a composition comprising a virus-like particle (“VLP”) and Murabutide.

Description

[0001]This invention was made with government support under grant 1 U19 AI062150-01 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention relates generally to vaccines. More particularly, it concerns compositions of antigens and adjuvants, and methods of their use. In specific embodiments, the invention concerns compositions comprising virus-like particle (“VLP”) antigens and Murabutide.[0004]2. Description of Related Art[0005]Virus-like particles (“VLPs”) typically consist of assembled protein subunits of a pathogenic virus that are capable of inducing an anti-viral (protective or therapeutic) immune response when administered to a subject, but are devoid of some or all of the nucleic acids necessary for viral replication. Thus, VLPs embody the best features of immunization with live or attenuated viruses, namely the induction of a relevant immune respons...

AI Technical Summary

Benefits of technology

[0015]In certain aspects, the present invention provides a method of enhancing the immunogencity of an antigen in a subject comprising contacting a mucosal surface of the subject with the antigen and a NOD agonist, wherein an immune response to the antigen is enhanced as compared to an immune response elicited by the antigen when administered without the NOD agonist. In certain aspects, the method further comprises contacting the mucosal surface of the subject with a TLR agonist.

[0021]The antigen and the adjuvant (NOD agonist and / or TLR agonist) may be combined in a single composition or they can be in separate compositions. When provided as separate compositions, the antigen and adjuvant may be administered at the same time or at different times. The composition may comprise a pharmaceutically acceptable carrier. In some embodiments, the carrier is a mucoadhesive. Mucoadhesives aid in retaining the antigen at or near the mucosa for a sufficient period of time to ensure adequate bioavailability of the antigen. The mucoadhesive may be a polymer, such as a polyethylene oxide homopolymer, poly vinyl pyrrolidone (PVP), methyl cellulose (MC), sodium carboxy methylcellulose (SCMC), hydroxy propyl cellulose (HPC), Carbopol, polyacrylate, chitosan, or polysaccharide. In one embodiment, the mucoadhesive is derived from Aloe vera polyshaccharides. The mucoadhesive polymer may be hydrophilic or a hydrogel.

Problems solved by technology

Thus, VLPs embody the best features of immunization with live or attenuated viruses, namely the induction of a relevant immune response, but lack the potential for causing disease because of the inability of the VLP to replicate in the subject.

While the immunogenicity and potential clinical benefit of VLPs have been demonstrated, as with any vaccine antigen, VLP immunogenicity might not always be sufficiently strong to mount a protective response—that is, an immune response might be induced by vaccination with a VLP antigen, but the strength, type and / or duration of the response might not be sufficiently robust to fend off disease upon a subject's exposure to the viral pathogen.

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