Polyvalent influenza virus-like particles (VLPS) and use as vaccines
Inventors
Assignees
United States, AS REPRESENTED BY SECRETARY DHHS • US Department of Health and Human Services
Publication Number
US-10130700-B2
Publication Date
2018-11-20
Expiration Date
2035-05-08
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Abstract
This disclosure provides compositions that include a mixture of viral like particles (VLPs), expressing different individual influenza hemagglutinin (HA) proteins that elicit broadly reactive immune responses to a wide variety of influenza viruses. For example, the composition can include at least two different influenza VLPs, a first VLP comprising a first HA polypeptide and a second VLP comprising a second influenza HA polypeptide, wherein the first and the second HA polypeptide are different subtypes and/or are from different influenza viruses, and a pharmaceutically acceptable carrier and/or an adjuvant. Methods of using the disclosed polymeric influenza VLP compositions to stimulate an immune response against influenza viruses, for example as a pre-pandemic or a seasonal vaccine, are provided.
Core Innovation
This disclosure provides compositions comprising a mixture of viral like particles (VLPs) each expressing different individual influenza hemagglutinin (HA) proteins. These compositions elicit broadly reactive immune responses to a wide variety of influenza viruses. For example, the compositions include at least two different influenza VLPs, a first comprising a first HA polypeptide and a second comprising a second HA polypeptide. These HA polypeptides are different subtypes and/or from different influenza viruses, optionally combined with a pharmaceutically acceptable carrier or an adjuvant.
The invention addresses the significant public health burden posed by influenza viruses, including influenza A and B, which cause substantial annual morbidity and mortality and have the potential to cause pandemics. There is a current need for broadly reactive or universal vaccines that provide protection beyond defined seasonal variants, particularly against zoonotic and pandemic strains with novel HA and NA subtypes. Available vaccines, such as inactivated intramuscular vaccines and live attenuated influenza vaccines, have limitations, including poor mucosal immune response induction and risks associated with reassortment. The disclosed compositions provide a safe, broadly reactive vaccine that elicits both mucosal and systemic immunity, using intranasal delivery of polyvalent VLPs each expressing a different HA subtype, optionally with neuraminidase (NA) and matrix proteins.
The compositions can be used as either universal pre-pandemic vaccines, providing protection against multiple influenza A HA subtypes (H1 to H16) and potentially NA subtypes, or as broadly reactive seasonal vaccines that also include influenza B HA subtypes from distinct antigenic lineages (Yamagata-like and Victoria-like). Production methods include transfection of mammalian cells or infection of insect cells with vectors encoding HA, NA, and matrix proteins. The methods of use include administering an effective amount of these polyvalent VLP compositions to elicit immune responses or immunize subjects, thus preventing infection and reducing disease severity from a wide array of influenza virus strains.
Claims Coverage
The patent includes multiple independent claims covering compositions, methods, and kits involving compositions of viral-like particles expressing different influenza HA and optionally NA subtypes.
Composition containing at least two different influenza VLPs with different HA polypeptides
A composition comprising at least two different influenza virus-like particles (VLPs), each comprising an individual type or subtype of hemagglutinin (HA) polypeptide, wherein the HA polypeptides are different subtypes and/or from different influenza viruses, providing heterosubtypic protection, combined with a pharmaceutically acceptable carrier.
Composition including influenza A and B HA polypeptides
Compositions wherein the first influenza HA polypeptide is an influenza A HA subtype (e.g., H1-H16) and the second influenza HA polypeptide is an influenza B HA polypeptide, such as from Yamagata-like or Victoria-like lineages.
Inclusion of influenza neuraminidase (NA) polypeptides in the composition
Compositions further comprising first and second VLPs expressing different influenza NA polypeptides, which may be from different subtypes or influenza viruses.
Compositions including influenza matrix proteins
Compositions wherein the influenza VLPs further comprise influenza matrix proteins, including influenza A M1 and M2 or influenza B M1 and BM2, associated with the respective HA or NA proteins.
Formulation and production methods
Compositions formulated for intranasal administration and prepared by transfection of host cells with vectors encoding the HA polypeptide or NA polypeptide and a vector encoding an influenza matrix polypeptide, under conditions to express HA, NA, and matrix proteins.
Methods of stimulating immune responses and immunization
Methods of eliciting an immune response or immunizing a subject against influenza virus by administering a therapeutically effective amount of the described compositions intranasally or by other routes, optionally specifying dosage ranges and subject types.
Kit comprising the composition and administration devices
A kit including containers comprising the composition and optionally containers with additional VLPs or adjuvants, syringes, or syringe atomizers for administration.
The independent claims focus on antigenically diverse influenza VLP compositions comprising different HA polypeptides from influenza A and/or B, optionally including NA and matrix proteins, formulated for safe administration (such as intranasal) to elicit broad immune protection. The claims cover compositions, methods of use for immunization or immune response elicitation, and kits for delivery.
Stated Advantages
The disclosed polyvalent VLPs are safe, non-infectious, and easy to manufacture and use.
They elicit broadly reactive immune responses providing protection against a wide variety of influenza A and B viruses, including heterologous and heterosubtypic strains.
Intranasal administration induces both mucosal and systemic immunity.
The compositions avoid problems associated with live attenuated influenza vaccines such as risk of reassortment.
The vaccine provides a broadly protective ‘universal’ pre-pandemic option and a more broadly reactive seasonal vaccine with inclusion of influenza B VLPs.
Documented Applications
Use as a broadly protective ‘universal’ pre-pandemic vaccine against diverse influenza A HA and NA subtypes.
Use as a seasonal vaccine including influenza A and B VLPs to provide broad immunity to circulating seasonal influenza strains.
Intranasal vaccination for stimulation of mucosal and systemic immune responses to influenza virus.
Use for immunizing subjects (humans, mammals, birds) against influenza infection to prevent illness or reduce disease severity.
Use in vaccine development and production, including kits with VLP compositions for administration.
Testing and protection demonstrated in animal models including mice and ferrets, and clinical trials in humans.
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