Vaccine compositions and methods of use

Abstract

The present disclosure provides vaccine compositions comprising at least one adjuvant and at least one antigen, wherein the adjuvant is a cationic lipid. The disclosure also provides methods of treating a disease in a mammal, methods of preventing a disease in a mammal, and methods of effecting antigen cross presentation to induce a humoral immune response and a cellular immune response in a mammal utilizing the vaccine compositions. Cross presentation of various antigens can be achieved by formulating the specific antigens with cationic lipids possessing adjuvant properties.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit under 35 USC §119(e) of U.S. Provisional Application Ser. No. 61 / 703,814, filed on Sep. 21, 2012, the entire disclosure of which is incorporated herein by reference.TECHNICAL FIELD[0002]Despite an increasing amount of research and interest in the field of immunology, there is currently a lack of vaccines that are adequately effective against various infectious pathogens or diseases such as malaria, HIV, hepatitis C, influenza, and tuberculosis. For example, current influenza vaccines induce antibodies against two main surface proteins from the virus, hemagglutinin and neuraminidase. Thus, current influenza vaccines only effectively protect against infection by strains of the virus that express versions of these proteins present in the vaccine. However, these two surface proteins frequently change as a consequence of mutations and re-assortment. Accordingly, influenza vaccines must be reformulated each y...

AI Technical Summary

Benefits of technology

The patent text describes a new influenza vaccine composition that can provide cross-protective immunity to different subtypes of the virus and can also serve as a universal vaccine against multiple strains. The vaccine composition enhances both humoral and cell-mediated responses and can provide a simple adjuvant platform for developing a new generation of simple vaccines that do not require adjuvant combinations or viral vectors. Additionally, the vaccine composition provides a new approach to developing a universal influenza vaccine without the need for multiple T-cell epitope peptides due to the enhanced cellular CD8+ T-cell response.

Problems solved by technology

As described above, immunity has been difficult to induce against the proteins found in emerging strains of influenza, such as those in H5N1 viruses that cause avian flu.

It is commonly believed that difficulties occur partly because of the existence of memory cells that can recognize annual, but not new, viral strains.

However, these approaches do not provide cross-reactivity to distinct subtypes of the virus.

Several other infections, such as hepatitis, HIV, and malaria, for example, exist for which antibodies provide insufficient protection.

Aluminum salts, however, do not directly induce signaling through TLRs and do not stimulate IL-12 production by DCs.

As described above, although some adjuvants such as the cationic lipids and MPL can elicit T-cell responses when formulated with peptides, the use of peptide fragments rather than whole antigens is a severe limitation because different peptide fragments are recognized by the T cells of different individuals.

In addition, the ability of peptides to elicit protective antibody responses is known to be weak and non-existent with several peptides.

However, existing inactivated vaccines like Fluzone consist of mostly HA protein and yet do not generate significant CD8 T cell responses.

In contrast, however, vaccines using the same antigen with aluminum hydroxide and MPL (AS04) or in an oil-in-water emulsion (AS03) induced high levels of antibody but failed to protect against infection.

Although live attenuated viral and bacterial vaccines can activate all arms of the immune system, adjuvants have so far not reached this goal.

However, such multiple adjuvant systems are complex and have the potential for formulation and safety difficulties.

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