Broadly protective inactivated influenza virus vaccine

A technology of influenza virus and influenza A virus, applied in antiviral agents, virus/bacteriophage, antibody medical components, etc.

Pending Publication Date: 2020-09-04
UNITED STATES OF AMERICA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A major difficulty faced by a universal influenza vaccine approach is the antigenic variability of the different HA and NA subtypes

Method used

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  • Broadly protective inactivated influenza virus vaccine
  • Broadly protective inactivated influenza virus vaccine
  • Broadly protective inactivated influenza virus vaccine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0162] Example 1: Chemically Inactivated Influenza Virus Mixture as a Universal Influenza Vaccine

[0163] This example describes a study evaluating an influenza virus vaccine consisting of a mixture of BPL-inactivated low pathogenicity avian influenza virus subtypes. The first vaccine mixture includes influenza viruses with HA subtypes H1, H3, H5, and H7, and the second vaccine mixture includes influenza viruses with HA subtypes H2, H4, H9, and H10 (see image 3 ). The influenza virus used in the assay is monovalent (eg, only includes a single or separate subtype of HA.

[0164] A quadrivalent vaccine (A / mallard / Ohio / 265 / 1987(H1N9), A / pintail / Ohio / 339 / 1987(H3N8), A / mallard / Maryland / 802 / 2007 (H5N1) and A / Environment / Maryland / 261 / 2006 (H7N3)) were compared with virus-like particle (VLP) vaccines comprising VLPs expressing HA from the same virus. figure 1Reciprocal HAI titers of mice vaccinated with quadrivalent influenza VLP vaccine or with BPL-inactivated whole virus quadr...

Embodiment 2

[0170] Example 2: Testing of Inactivated Influenza Virus Vaccines in Ferrets

[0171] Not infected by influenza (influenza ) Purebred ferrets (Mustela putorius furo, female, 6-12 months old) were purchased from Marshall Farms (Sayre, PA, USA). Ferrets were housed in pairs in stainless steel cages (Shor-line, Kansas City, KS, USA) including Sani-chips Laboratory Animal Bedding (P.J. Murphy Forest Products, Montville, NJ, USA). ). Ferrets were provided the Teklad Global Ferret Diet (Harlan Teklad, Madison, WI, USA) and had water ad libitum.

[0172] Ferrets were blank vaccinated or IN or IM with a quadrivalent vaccine consisting of 4 different BPL-inactivated whole influenza viruses: A / mallard / Ohio / 265 / 1987(H1N9), A / pintail / Ohio / 339 / 1987 (H3N8), A / mallard / Maryland / 802 / 2007 (H5N1), and A / Environment / Maryland / 261 / 2006 (H7N3). Two ferrets were included in each vaccination group. Ferrets were challenged with antigenic variant and pathogenic strains A / Port Chalmers / 1971 (H3N2)...

Embodiment 3

[0178] Example 3: Human Clinical Trials

[0179] After selecting the best broadly cross-reactive inactivated influenza virus vaccine in laboratory animals, it was studied in human volunteers. In some instances, the vaccine will include an adjuvant suitable for human use.

[0180] Will be produced using GMP methods (e.g. tetravalent H1 / H3 / H5 / H7, tetravalent H2 / H4 / H9 / H10 or octavalent H1 / H3 / H5 / H7 / H2 / H4 / H9 / H10) including inactivation (e.g. BPL-inactivated) whole influenza vaccine formulation and administered intranasally to humans. Those of skill in the art will appreciate that other inactivated influenza virus vaccine compositions provided herein can be similarly tested.

[0181] Briefly, humans were vaccinated intranasally with influenza vaccine compositions. The human is boosted with the same mixture about 3-12 weeks later (eg, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 weeks later). A second group of people is blank vaccinated (eg, with saline). Obtain and store blood and nasal s...

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Abstract

Universal influenza virus vaccine compositions that include multiple inactivated influenza A viruses are described. The compositions include four or more different influenza A viruses, each virus having a different hemagglutinin (HA) subtype. The vaccine compositions can be used, for example, to elicit an immune response against influenza virus, to immunize a subject against seasonal influenza virus, and/or mitigate a future pandemic by serving as a pre-pandemic vaccine.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 620,051, filed January 22, 2018, which is hereby incorporated by reference in its entirety. technical field [0003] The present disclosure relates to compositions comprising a mixture of inactivated, low pathogenic influenza virus strains, and their use to elicit broadly reactive immune responses against seasonal influenza and to suppress zoonotic influenza pandemics. Background technique [0004] Influenza viruses are members of the Orthomyxoviridae family. There are three types of influenza viruses, called influenza A, B, and C. Influenza A viruses infect not only humans, but also many birds and mammals, and are classified by subtypes of their surface proteins, hemagglutinin (HA) and neuraminidase (NA). Influenza A virions contain a segmented negative-sense RNA genome that encodes the following proteins: hemagglutinin (HA), neuraminidase (N...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/145A61K39/295C12N7/00A61P31/16
CPCA61K39/145A61K39/295C12N7/00A61P31/16A61K2039/5252A61K2039/543
Inventor J·K·陶本伯格L·M·施瓦茨曼
Owner UNITED STATES OF AMERICA
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