Ras pathways as markers of protection against HIV and methods to improve vaccine efficacy
Inventors
Franchini, Genoveffa • Sekaly, Rafick-Pierre • Fourati, Slim • Cameron, Mark • Vaccari, Monica • Schifanella, Luca • Gordon, Shari • Doster, Melvin • Liyanage, Namal Malimbada
Assignees
Oregon Health and Science University • US Department of Health and Human Services
Publication Number
US-10398772-B2
Publication Date
2019-09-03
Expiration Date
2035-01-08
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Abstract
Compositions including a therapeutically effective amount of an HIV immunogen in combination with an agent that stimulates the Ras pathway, wherein the agent is not an aluminum salt, are disclosed. Methods are also disclosed for inducing an immune response to HIV, and/or to inhibit or treat HIV infection, in a subject, using an HIV immunogen and an agent that stimulates the Ras pathway. Methods also are disclosed for determining if an immunogenic composition will induce a protective response, and/or to determine if an immunogenic composition is of use to prevent or treat an HIV infection. The methods including determining if the immunogenic composition increases the level of one or more components of the Ras signaling pathway.
Core Innovation
The invention provides compositions including a therapeutically effective amount of an HIV immunogen combined with an agent that stimulates the Ras pathway, excluding aluminum salts. These compositions are designed to induce an enhanced immune response to HIV. Methods are disclosed for inducing such immune responses in a subject, for inhibiting or treating HIV infection, and for determining if an immunogenic composition will induce a protective response or be useful in prevention or treatment of HIV infection by assessing the modulation of Ras pathway components.
The problem addressed is the continuing high incidence and mortality of HIV despite available antiretroviral therapies, highlighting a need for more effective vaccines and adjuvants. Existing adjuvants like Alum are limited in efficacy, and while MF59 shows some improvements in immune response, it does not adequately induce protection against HIV. There remains a need for adjuvants that can improve the immune response to HIV immunogens and assays that can predict vaccine-induced protective responses.
Claims Coverage
The patent contains 2 independent claims covering an immunogenic composition and methods of inducing an immune response to HIV using specific components.
Immunogenic composition comprising HIV immunogen and Ras pathway-stimulating agent
An immunogenic composition comprising an effective amount of an HIV immunogen or its encoding nucleic acid, combined with an effective amount of an agent that stimulates the Ras pathway, wherein the agent is epidermal growth factor (EGF), insulin like growth factor (IGF), or a functional fragment or variant thereof, or combinations thereof.
Method of inducing an immune response using the immunogenic composition
A method for inducing an immune response to HIV in a subject by administering a therapeutically effective amount of the said immunogenic composition, where the agent stimulates the Ras pathway and may be administered simultaneously or sequentially with the HIV immunogen or its nucleic acid.
The claims cover compositions combining an HIV immunogen with agents stimulating the Ras pathway, specifically EGF and IGF or their functional variants, and methods of inducing protective immune responses to HIV using these compositions, emphasizing modes of administration and inclusion of nucleic acid vectors such as poxviral vectors.
Stated Advantages
Modulation of the Ras pathways can be a predictive biomarker of vaccine efficacy.
Activation of Ras before, during, or after vaccination can be used as an adjuvant to increase vaccine protection.
Documented Applications
Use of immunogenic compositions comprising an HIV immunogen and an agent that stimulates the Ras pathway to induce an immune response against HIV in a subject.
Methods for detecting the likelihood that an immunogenic composition will induce a protective immune response against HIV by assessing the level of Ras signaling pathway components in biological samples.
Methods for inhibiting or treating HIV infection in subjects by administering the compositions.
Use of Ras pathway stimulatory agents as adjuvants in HIV vaccine formulations to improve vaccine efficacy.
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