Vaccines for use in the prophylaxis and treatment of influenza virus disease

Abstract

Provided herein are polypeptides comprising portions of the influenza virus hemagglutinin, compositions comprising such polypeptides that can be used as immunogens in vaccines and methods of their use to generate an immune response against multiple influenza subtypes in a subject.

Description

[0001]This application claims priority benefit of U.S. provisional application No. 61 / 305,898, filed Feb. 18, 2010, U.S. nonprovisional application Ser. No. 12 / 788,103, filed May 26, 2010, U.S. provisional application No. 61 / 354,160, filed Jun. 11, 2010 and U.S. provisional application No. 61 / 385,083, filed Sep. 21, 2010, each of which is incorporated herein by reference in its entirety.[0002]This invention was made with United States Government support under award numbers U01 A1070469-02 and 1RC1 A1086061-01 awarded by the National Institutes of Health (NIH). The United States Government has certain rights in this invention.1. INTRODUCTION[0003]Provided herein are polypeptides comprising portions of the influenza virus hemagglutinin, compositions comprising such polypeptides that can be used as immunogens in vaccines and methods of their use to generate an immune response against multiple influenza subtypes in a subject.2. BACKGROUND[0004]Influenza viruses are enveloped RNA viruses...

AI Technical Summary

Benefits of technology

[0010]The invention is based, in part, on the design of flu polypeptides that mimic the structure and function / activity of the long alpha helix region of the HA2 subunit of influenza hemagglutinin. Surprisingly, immunization with a flu polypeptide corresponding to the HA2 long alpha helix of a particular influenza subtype induces serum antibodies that cross-react with hemagglutinin from multiple influenza subtypes. The data described herein also demonstrate that animals immunized with a flu polypeptide corresponding to the HA2 long alpha helix of one particular subtype are protected against lethal influenza viral challenges with different influenza virus subtypes. Accordingly, the flu polypeptides provided herein may be used in immunogenic compositions (e.g., vaccines) capable of generating immune responses against a plurality of different influenza strains and subtypes—in other words, a “universal” flu vaccine.

[0050]As used herein, the terms “treat,”“treatment,” and “treating” refer in the context of administration of a therapy(ies) to a subject to treating an influenza virus disease to obtain a beneficial or therapeutic effect of a therapy or a combination of therapies. In specific embodiments, such terms refer to one, two, three, four, five or more of the following effects resulting from the administration of a therapy or a combination of therapies: (i) the reduction or amelioration of the severity of an influenza virus infection or a disease or a symptom associated therewith; (ii) the reduction in the duration of an influenza virus infection or a disease or a symptom associated therewith; (iii) the regression of an influenza virus infection or a disease or a symptom associated therewith; (iv) the reduction of the titer of an influenza virus; (v) the reduction in organ failure associated with an influenza virus, infection or a disease associated therewith; (vi) the reduction in hospitalization of a subject; (vii) the reduction in hospitalization length; (viii) the increase in the survival of a subject; (ix) the elimination of an influenza virus infection or a disease or symptom associated therewith; (x) the inhibition of the progression of an influenza virus infection or a disease or a symptom associated therewith; (xi) the prevention of the spread of an influenza virus from a cell, tissue, organ or subject to another cell, tissue, organ or subject; (xii) the inhibition or reduction in the entry of an influenza virus into a host cell(s); (xiii) the inhibition or reduction in the replication of an influenza virus genome; (xiv) the inhibition or reduction in the synthesis of influenza virus proteins; (xv) the inhibition or reduction in the release of influenza virus particles from a host cell(s); and / or (xvi) the enhancement or improvement the therapeutic effect of another therapy.

Problems solved by technology

Influenza A and B viruses are major human pathogens, causing a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia which can result in death.

The cumulative morbidity and mortality caused by seasonal influenza is substantial due to the relatively high rate of infection.

In addition to annual epidemics, influenza viruses are the cause of infrequent pandemics.

Lancet 351: 472-7), there have been concerns that the virus may become transmissible between humans and cause a major pandemic.

Such a match is often difficult to attain due to a combination of factors.

Occasionally, the predictions of the vaccine strain selection committee are inaccurate, resulting in a substantial drop in the efficacy of vaccination.

The possibility of a novel subtype of influenza A virus entering the human population also presents a significant challenge to current vaccination strategies.

Since it is impossible to predict what subtype and strain of Influenza virus will cause the next pandemic, current, strain-specific approaches cannot be used to prepare a pandemic influenza vaccine.

In certain embodiments, the effective amount does not result in complete protection from an influenza virus disease, but results in a lower titer or reduced number of influenza viruses compared to an untreated subject.

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