Compositions and methods for diagnosing and/or treating influenza infection
The present invention provides HA polypeptides (e.g., H1 HA polypeptides) that bind to umbrella-topology glycans, and reagents and methods relating thereto. The present invention provides binding agents that bind to HA polypeptides (e.g., H1 HA polypeptides), and reagents and methods relating thereto. The present invention provides interfering agents that inhibit the binding of HA polypeptides (e.g., H1 HA polypeptides) to HA receptors, and reagents and methods relating thereto. The present invention provides compositions and methods for treating, preventing, and/or diagnosing influenza infection utilizing HA polypeptides, HA polypeptide binding agents, HA polypeptide interfering agents, and/or vaccine compositions comprising any of the foregoing.
1. A method of detecting an H1 HA influenza hemagglutinin (“HA”) polypeptide variant in a sample, the method comprising steps of:
contacting a patient sample with a binding agent specific for an H1 HA influenza hemagglutinin (“HA”) polypeptide variant whose amino acid sequence:
i) shows at least 90% identity with a reference wild type H1 HA polypeptide that is the HA from A/California/04/2009 strain (SEQ ID NO: 46);
ii) includes a sequence substitution relative to the reference at each of the following positions:
Position
Amino acid
(corresponding to
residue
wild type H3 HA
in reference
186
Ser
189
Ala
219
Ile
227
Glu
iii) differs from that of each of ADA76, A/duck/Alberta/35/76 (H1N1) (SEQ ID NO: 23); ASI30, A/Swine/Iowa/30 (H1N1) (SEQ ID NO: 24); APR34, A/Puerto Rico/8/34 (H1N1) (SEQ ID NO: 25); ASC18, A/South Carolina/1/18 (H1N1) (SEQ ID NO: 26); AT91, A/Texas/36/91 (H1N1) (SEQ ID NO: 27); ANY18, A/New York/1/18 (H1N1) (SEQ ID NO: 28); ADU63, A/Duck/Ukraine/1/63 (H3N8) (SEQ ID NO: 29); AAI68, A/Aichi/2/68 (H3N2) (SEQ ID NO: 30); AM99, A/Moscow/10/99 (H3N2) (SEQ ID NO: 31); ADS97, A/Duck/Singapore/3/97 (H5N3) (SEQ ID NO: 32); Viet04, A/Vietnam/1203/2004 (H5N1) (SEQ ID NO: 33); and
detecting binding in the sample.
2. The method of claim 1 , where in the sample is or comprises one or more of blood, serum/plasma, peripheral blood mononuclear cells/peripheral blood lymphocytes (PBMC/PBL), sputum, urine, feces, throat swabs, dermal lesion swabs, cerebrospinal fluids, cervical smears, pus samples, food matrices, and tissues from various parts of the body such as brain, spleen, and liver.
3. The method of claim 1 , wherein the sample is from a patient who has previously been exposed to one or more viruses showing similarity with 2009 A/H1N1.
4. A method of detecting influenza, the method comprising steps of:
contacting an environmental sample with a binding agent specific for an H1 HA influenza hemagglutinin (“HA”) polypeptide variant whose amino acid sequence:
i) shows at least 90% identity with a reference wild type H1 HA polypeptide that is the HA from A/California/04/2009 strain (SEQ ID NO: 46);
ii) includes a sequence substitution relative to the reference at each of the following positions:
Position
Amino acid
(corresponding to
residue
wild type H3 HA)
in reference
186
Ser
189
Ala
219
Ile
227
Glu
iii) differs from that of each of ADA76, A/duck/Alberta/35/76 (H1N1) (SEQ ID NO: 23); ASI30, A/Swine/Iowa/30 (H1N1) (SEQ ID NO: 24); APR34, A/Puerto Rico/8/34 (H1N1) (SEQ ID NO: 25); ASC18, A/South Carolina/1/18 (H1N1) (SEQ ID NO: 26); AT91, A/Texas/36/91 (H1N1) (SEQ ID NO: 27); ANY18, A/New York/1/18 (H1N1) (SEQ ID NO: 28); ADU63, A/Duck/Ukraine/1/63 (H3N8) (SEQ ID NO: 29); AAI68, A/Aichi/2/68 (H3N2) (SEQ ID NO: 30); AM99, A/Moscow/10/99 (H3N2) (SEQ ID NO: 31); ADS97, A/Duck/Singapore/3/97 (H5N3) (SEQ ID NO: 32); Viet04, A/Vietnam/1203/2004 (H5N1) (SEQ ID NO: 33); and
detecting binding of the binding agent to the sample.
5. The method of claim 4 , wherein the environmental sample is or comprises one or more of soil, water and flora.