Search

US-20260124292-A1 - MULTIEPITOPE UNIVERSAL INFLUENZA VACCINE

US20260124292A1US 20260124292 A1US20260124292 A1US 20260124292A1US-20260124292-A1

Abstract

Polyepitope vaccine formulations relating to at least 5 of influenza A virus (IAV) derived peptides capable of inducing IFNγ by CD8+ T cells selected from the group of peptides with amino acid sequences SEQ ID NO:1 (ILRGSVAHK), SEQ ID NO:2 (ELRSRYWAI), SEQ ID NO:3 (SRYWAIRTR), SEQ ID NO:4 (CTELKLSDY), SEQ ID NO:5 (GILGFVFTL), SEQ ID NO:6 (SIIPSGPLK), SEQ ID NO:7 (ASCMGLIY), SEQ ID NO:8 (FMYSDFHFI), SEQ ID NO:9 (FVRQCFNPM), SEQ ID NO:10 (VSDGGPNLY), SEQ ID NO:11 (FLKDVMESM), SEQ ID NO:12 (NMLSTVLGV), SEQ ID NO:13 (MMMGMFNML), SEQ ID NO:14 (YSHGTGTGY), SEQ ID NO:15 (HSNLNDATY), SEQ ID NO:16 (RRSGAAGAAVK), SEQ ID NO:17 (LLTEVETYV), SEQ ID NO:18 (MVLASTTAK), SEQ ID NO:19 (RGINDRNFW) and SEQ ID NO:20 (FLLMDALKL).

Inventors

  • Sharmistha Dam
  • Gustaaf Frank Rimmelzwaan
  • Albertus Dominicus Marcellinus Erasmus Osterhaus

Assignees

  • University of Veterinary Medicine Hannover, Foundation

Dates

Publication Date
20260507
Application Date
20230922
Priority Date
20220923

Claims (20)

  1. 1 .- 16 . (canceled)
  2. 17 . A polynucleotide encoding at least a polyepitope polypeptide having at least five influenza A virus (IAV)-derived peptides that induce IFNγ by CD8+ T cells, the at least five IAV-derived peptides having SEQ ID NO:8 (FMYSDFHFI), SEQ ID NO:9 (FVRQCFNPM), SEQ ID NO:12 (NMLSTVLGV), SEQ ID NO:13 (MMMGMFNML), and SEQ ID NO:14 (YSHGTGTGY), wherein the polynucleotide also has genetic information that provides peptide spacer (linker) placement adjacent to IAV-derived peptides, and wherein the polynucleotide has a polynucleotide encoding a degron.
  3. 18 . The polynucleotide of claim 17 encoding a further five IAV-derived peptides that induce IFNγ by CD8+ T cells, the further five peptides having SEQ ID NO:5 (GILGFVFTL), SEQ ID NO:3 (SRYWAIRTR), SEQ ID NO:16 (RRSGAAGAAVK), SEQ ID NO:2 (ELRSRYWAI), and SEQ ID NO:4 (CTELKLSDY).
  4. 19 . The polynucleotide of claim 17 encoding at least 15 IAV-derived peptides that induce IFNγ by CD8+ T cells, the 15 IAV-derived peptides selected from the group consisting of SEQ ID NO:1 (ILRGSVAHK), SEQ ID NO:2 (ELRSRYWAI), SEQ ID NO:3 (SRYWAIRTR), SEQ ID NO:4 (CTELKLSDY), SEQ ID NO:5 (GILGFVFTL), SEQ ID NO:6 (SIIPSGPLK), SEQ ID NO:7 (ASCMGLIY), SEQ ID NO:8 (FMYSDFHFI), SEQ ID NO:9 (FVRQCFNPM), SEQ ID NO:10 (VSDGGPNLY), SEQ ID NO:11 (FLKDVMESM), SEQ ID NO:12 (NMLSTVLGV), SEQ ID NO:13 (MMMGMFNML), SEQ ID NO:14 (YSHGTGTGY), SEQ ID NO:15 (HSNLNDATY), SEQ ID NO:16 (RRSGAAGAAVK), SEQ ID NO:17 (LLTEVETYV), SEQ ID NO:18 (MVLASTTAK), SEQ ID NO:19 (RGINDRNFW), and SEQ ID NO:20 (FLLMDALKL).
  5. 20 . The polynucleotide of claim 17 encoding 20 IAV-derived peptides that induce IFNγ by CD8+ T cells, with amino acid sequences SEQ ID NO:1 (ILRGSVAHK), SEQ ID NO:2 (ELRSRYWAI), SEQ ID NO:3 (SRYWAIRTR), SEQ ID NO:4 (CTELKLSDY), SEQ ID NO:5 (GILGFVFTL), SEQ ID NO:6 (SIIPSGPLK), SEQ ID NO:7 (ASCMGLIY), SEQ ID NO:8 (FMYSDFHFI), SEQ ID NO:9 (FVRQCFNPM), SEQ ID NO:10 (VSDGGPNLY), SEQ ID NO:11 (FLKDVMESM), SEQ ID NO:12 (NMLSTVLGV), SEQ ID NO:13 (MMMGMFNML), SEQ ID NO:14 (YSHGTGTGY), SEQ ID NO:15 (HSNLNDATY), SEQ ID NO:16 (RRSGAAGAAVK), SEQ ID NO:17 (LLTEVETYV), SEQ ID NO:18 (MVLASTTAK), SEQ ID NO:19 (RGINDRNFW), and SEQ ID NO:20 (FLLMDALKL).
  6. 21 . The polynucleotide of claim 17 , wherein the peptide spacer (linker) comprises tripeptide AAY.
  7. 22 . The polynucleotide of claim 17 , wherein the degron comprises ubiquitin.
  8. 23 . A nucleic acid vector, virus, cell, or formulation comprising the polynucleotide of claim 17 .
  9. 24 . A proteinaceous formulation comprising a polyepitope polypeptide derived from the polynucleotide of claim 17 .
  10. 25 . A polyepitope polypeptide comprising: at least five influenza A virus (IAV)-derived peptides that induce IFNγ by CD8+ T cells, wherein the at least five IAV-derived peptides are SEQ ID NO:8 (FMYSDFHFI), SEQ ID NO:9 (FVRQCFNPM), SEQ ID NO:12 (NMLSTVLGV), SEQ ID NO:13 (MMMGMFNML), and SEQ ID NO:14 (YSHGTGTGY), an appropriate peptide spacer (linker) placement adjacent to IAV-derived peptides, and a degron.
  11. 26 . The polyepitope polypeptide of claim 25 further comprising a further five IAV-derived peptides that induce IFNγ by CD8+ T cells, wherein the further five IAV-derived peptides are SEQ ID NO:5 (GILGFVFTL), SEQ ID NO:3 (SRYWAIRTR), SEQ ID NO:16 (RRSGAAGAAVK), SEQ ID NO:2 (ELRSRYWAI), and SEQ ID NO:4 (CTELKLSDY).
  12. 27 . The polyepitope polypeptide of claim 25 , comprising at least 15 IAV-derived peptides capable of inducing IFNγ by CD8+ T cells selected from the group consisting of SEQ ID NO:1 (ILRGSVAHK), SEQ ID NO:2 (ELRSRYWAI), SEQ ID NO:3 (SRYWAIRTR), SEQ ID NO:4 (CTELKLSDY), SEQ ID NO:5 (GILGFVFTL), SEQ ID NO:6 (SIIPSGPLK), SEQ ID NO:7 (ASCMGLIY), SEQ ID NO:8 (FMYSDFHFI), SEQ ID NO:9 (FVRQCFNPM), SEQ ID NO:10 (VSDGGPNLY), SEQ ID NO:11 (FLKDVMESM), SEQ ID NO:12 (NMLSTVLGV), SEQ ID NO:13 (MMMGMFNML), SEQ ID NO:14 (YSHGTGTGY), SEQ ID NO:15 (HSNLNDATY), SEQ ID NO:16 (RRSGAAGAAVK), SEQ ID NO:17 (LLTEVETYV), SEQ ID NO:18 (MVLASTTAK), SEQ ID NO:19 (RGINDRNFW), and SEQ ID NO:20 (FLLMDALKL).
  13. 28 . The polyepitope polypeptide of claim 25 , comprising 20 IAV-derived peptides that induce IFNγ by CD8+ T cells, with amino acid sequences SEQ ID NO:1 (ILRGSVAHK), SEQ ID NO:2 (ELRSRYWAI), SEQ ID NO:3 (SRYWAIRTR), SEQ ID NO:4 (CTELKLSDY), SEQ ID NO:5 (GILGFVFTL), SEQ ID NO:6 (SIIPSGPLK), SEQ ID NO:7 (ASCMGLIY), SEQ ID NO:8 (FMYSDFHFI), SEQ ID NO:9 (FVRQCFNPM), SEQ ID NO:10 (VSDGGPNLY), SEQ ID NO:11 (FLKDVMESM), SEQ ID NO:12 (NMLSTVLGV), SEQ ID NO:13 (MMMGMFNML), SEQ ID NO:14 (YSHGTGTGY), SEQ ID NO:15 (HSNLNDATY), SEQ ID NO:16 (RRSGAAGAAVK), SEQ ID NO:17 (LLTEVETYV), SEQ ID NO:18 (MVLASTTAK), SEQ ID NO:19 (RGINDRNFW), and SEQ ID NO:20 (FLLMDALKL).
  14. 29 . An antigenic or immunogenic formulation comprising the polynucleotide of claim 17 .
  15. 30 . A vaccine formulation produced by mixing the antigenic or immunogenic formulation of claim 29 with a pharmaceutically acceptable excipient.
  16. 31 . A method of treating a subject to generate a humoral vaccine response toward an influenza virus hemagglutinin protein, the method comprising: administering to the subject the vaccine formulation of claim 30 together with, in addition to, or concomitant with a vaccine directed at generating a humoral vaccine response toward an influenza virus hemagglutinin protein.
  17. 32 . An antigenic formulation comprising the polyepitope polypeptide of claim 25 .
  18. 33 . An immunogenic formulation comprising the polyepitope polypeptide claim 25 .
  19. 34 . A vaccine formulation produced by mixing the immunogenic formulation of claim 33 with a pharmaceutically acceptable excipient.
  20. 35 . A method of treating a subject to generate a humoral vaccine response toward an influenza virus hemagglutinin protein, the method comprising: administering to the subject the vaccine formulation of claim 30 together with, in addition to, or concomitant with a vaccine directed at generating a humoral vaccine response toward an influenza virus hemagglutinin protein.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a national phase entry under 35 U.S.C. § 371 of International Patent Application PCT/EP2023/076265, filed Sep. 22, 2023, designating the United States of America and published as International Patent Publication WO 2024/062106 A1 on Mar. 28, 2024, which claims the benefit under Article 8 of the Patent Cooperation Treaty of European Patent Application Serial No. 22197406.6, filed Sep. 23, 2022. TECHNICAL FIELD The disclosure relates to the field of vaccination against influenza virus infections with broad spectrum influenza vaccines. BACKGROUND Influenza is a common acute respiratory disease due to a virus that causes annual seasonal epidemics. Three major pandemics occurred in the 20th century, 1918-1919, 1957 and 1968, and one in 2009, mainly due to genetic variants of type A influenza virus (IAV). In temperate regions the incidence of hospitalization increases during annual influenza epidemics. More than 90% of deaths linked to influenza involve people over 65 years of age. Yearly vaccination is the main preventive measure in this age group. Yearly vaccination is also recommended for younger people with serious chronic disease. Preferably, the vaccine strains closely match the epidemic strains circulating at the time of vaccination antigenically to afford optimal protection. In relative terms, vaccination of people over 65 reduces the number of deaths linked to influenza by up to 80%, hospitalization and pneumonia by up to 50%, and symptomatic influenza by up to 30%. The full impact of influenza is increasingly recognized as an illness that goes well beyond pneumonia and influenza statistics. Peak months of mortality due to respiratory illness, ischemic heart disease, cerebrovascular events, and diabetes in adults 70 years and older coincide with annual influenza epidemics, suggesting that influenza illness is the major cause of excess mortality in this population during the winter months (McElhaney 2011). Vaccination programs using the current split-virus vaccines are cost-saving in the over 65 population even though these vaccines often fail to provide adequate protection in older adults and influenza illness continues to have devastating consequences in this population. Rising rates of hospitalization are anticipated from seasonal influenza and, in the event of a real pandemic in older people, threaten to paralyze the health and social systems of support. Development of vaccines is a priority to prepare for potential pandemics but is complicated by antigenic variation of the surface glycoprotein hemagglutinin (de Vries et al. 2018). Vaccination is the most appropriate countermeasure to control the spread of IAV and prevent disease. However, the lack of an efficacious method to predict the circulating strains sometimes leads to a mismatch between the annual vaccine and circulating viruses. To illustrate, the sudden emergence of the 2009 influenza A/H1N1 pandemic strain and the recent appearance of the highly pathogenic avian A/H7N9 strain in 2013 in China, underscores the unpredictable nature of the virus and the difficulty in comprehending the emergence of new strains. Two types of influenza vaccine are widely available: inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV). Traditionally, to cope with yearly varying antigenic variation, influenza vaccines (both IIV and LAIV) have been produced to protect against 3 or 4 different seasonal influenza viruses (also called trivalent or quadrivalent vaccines). Current quadrivalent vaccines contain components of influenza A(H3N2), A(H1N1) and 2 influenza lineages of influenza B virus. The trivalent or quadrivalent vaccines foremost rely on specific targeting of the major surface protein, hemagglutinin (HA), and are standardized as stimulating anti-HA antibodies as the primary correlate of protection, but these vaccines have limited and somewhat unpredictable efficacy, particularly in those that most require protection such as the elderly, young, and infirm. Regardless of the type or composition of seasonal influenza vaccine, vaccination needs be administered annually to provide optimal protection against infection. As influenza vaccine effectiveness can vary yearly due to the constant evolving nature of influenza viruses, including those circulating and infecting humans, these vaccines are updated regularly to antigenically match which influenza strains that are in circulation. The WHO organizes regular consultations with an advisory group of experts gathered from WHO Collaboration Centers and WHO Essential Regulatory Laboratories to analyze influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System. The recommendations issued are used by the national vaccine regulatory agencies and pharmaceutical companies to develop, produce, and license influenza vaccines for the following influenza season. Because of the evolving nature,