Archaeal polar lipid aggregates for administration to animals

Abstract

The invention provides non-replicating compositions, and methods for the delivery of these compositions containing pharmaceuticals, biologically relevant molecules, and / or antigens to the host, by administration via a mucosal route such as the intranasal. This invention provides non-replicating vaccine compositions and methods for the delivery of antigens in these vaccine compositions comprising an antigen and a self-adjuvanting carrier, useful for inducing antigen-specific mucosal and systemic immune responses in the host upon immunization via a mucosal route such as intranasal. The vaccine compositions comprise multivalent cations in association with a plurality of spherical archaeal polar lipid aggregates containing aqueous compartments, the AMVAD structure, formed by the interaction of archaeosomes and antigen(s) with multivalent cations such as Ca2+, wherein the AMVAD structure acts as a self-adjuvanting carrier for the antigen(s) in the vaccine composition. Certain advantageous immune responses can also be elicited with the subject compositions.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of provisional application Ser. No. 60 / 875,305, filed Dec. 15, 2006.FIELD OF THE INVENTION[0002]This invention relates in part to delivery of pharmaceuticals, biologically relevant molecules, and antigens to a host. It also relates to mucosal delivery, especially mucosal vaccine delivery. It relates to the use of vaccine compositions comprising archaeal polar lipid aggregates as mucosal vaccine delivery system for acellular (non-replicating), defined and mixed, antigens so as to elicit strong, protective, antigen-specific mucosal and antigen-specific systemic immune responses in the host, upon administration of the vaccine via mucosal routes. The invention also relates to the use of archaeal polar lipid aggregates as self-adjuvanting mucosal delivery systems for acellular antigens in vaccines administered via mucosal routes. Preferably, such administration elicits protective, antigen-specific systemic hu...

AI Technical Summary

Benefits of technology

[0047]Surprisingly and unexpectedly, it was presently discovered that by addition of multivalent cations or multivalent organic cationic compounds, archaeosomes can be formulated into structures comprising aggregates of individual, larger, spherical structures with aqueous compartments, referred to herein as archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) structures. It was also discovered that vaccine compositions consisting of antigens formulated into AMVAD structures elicited strong, sustained, and protective antigen-specific mucosal immunity upon administration (that is vaccination or immunization) to the host via a mucosal route such as the i.n. route. In addition to the mucosal immunity elicited at the immunization site and at other distal mucosal surfaces, strong systemic immune responses (humoral antibody and cell-mediated responses including antigen-specific CD8+ CTL responses) were also elicited by these formulations. The mucosal and systemic immune responses were sustained for a period of several months, and were subject to strong memory responses upon antigen alone boost. However, although systemic immunization with the AMVAD vaccine formulation elicited strong systemic immune responses, there was little to no elicitation of mucosal immune responses. In addition to strong, sustained mucosal and serum antigen-specific IgA antibody responses, the AMVAD vaccine formulation can elicit robust and sustained systemic antibody responses (serum IgG, IgG1, IgG2a) upon intranasal administration to the host. Additionally, strong antigen-specific CTL responses can also be elicited. All of these immune responses exhibit strong memory responses upon a booster immunization with the antigen alone. The invention provides methods for providing protective immunity in the vaccinated host against infections caused by mucosal pathogens, and in the treatment of disease conditions that are known to be mitigated by the elicitation of such immune responses. Compositions of the invention are also useful for eliciting systemic immune responses by systemic immunization, showing utility for systemic immunization for protection against pathogens / diseases requiring such host-immune responses for protection.

Problems solved by technology

However, although systemic immunization with the AMVAD vaccine formulation elicited strong systemic immune responses, there was little to no elicitation of mucosal immune responses.

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