Multivalent influenza nanoparticle vaccines
Inventors
BODDAPATI, Sarathi • HERWADKAR, Anushree • Wong, Jason • LIN, Yen-Huei • Smith, Gale • Tian, Jing-Hui
Assignees
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Publication Number
US-11896662-B2
Publication Date
2024-02-13
Expiration Date
Abstract
Disclosed herein are multivalent nanoparticle vaccine compositions suitable for use in influenza vaccines. The nanoparticles include effective amounts of influenza glycoproteins that provide increased immune responses compared to a commercially available influenza vaccine composition. The present disclosure also provides vaccine formulation strategies that are cost effective and are convenient for clinical use. Methods of administering the nanoparticle vaccine compositions to a subject are also disclosed.
Core Innovation
The patent discloses multivalent influenza nanoparticle vaccine compositions that include first and second HaSMaN (Hemagglutinin Saponin Matrix Nanoparticle) constructs. Each HaSMaN includes an ISCOM matrix particle defined by Quillaja Saponaria Molina saponin fractions, and a recombinant influenza hemagglutinin (HA) glycoprotein trimer associated through the HA tail while the HA head extends distally. The composition further includes a pharmaceutically acceptable buffer or carrier.
In one construct, the ISCOM matrix particle comprises Fraction A of Quillaja Saponaria Molina and not Fraction C, and in the other construct it comprises Fraction C and not Fraction A. Each HA is from a Type A influenza strain and each HA contains a transmembrane domain. The resulting composition supports the inclusion of two different HaSMaN nanoparticle constructs as a multivalent vaccine formulation.
The patent also discloses methods of preparing HaSMaN by combining a detergent core nanoparticle containing hemagglutinin (HA) with an ISCOM matrix particle for at least about four hours. The ISCOM matrix particle is specified to comprise either Fraction A and not Fraction C or Fraction C and not Fraction A, while the HA contains a transmembrane domain and is from a Type A influenza strain.
Claims Coverage
The independent claims cover one multivalent HaSMaN composition containing two different HaSMaN constructs with complementary ISCOM saponin fractions for Type A influenza HA that includes a transmembrane domain, and two alternative HaSMaN preparation methods distinguished by whether the ISCOM matrix particle uses Fraction A or Fraction C, each requiring Type A influenza HA with a transmembrane domain. Across the independent claims, the core inventive structure centers on pairing HA with an ISCOM matrix particle having mutually exclusive saponin fractions and requiring HA transmembrane domain association, plus preparation by combining HA-containing detergent core nanoparticles with ISCOM matrix particles for at least about four hours.
Two HaSMaN constructs with complementary ISCOM saponin fractions
A composition comprising a first HaSMaN having an ISCOM matrix particle comprising Fraction A of Quillaja Saponaria Molina and not Fraction C of Quillaja Saponaria Molina, and a second HaSMaN having an ISCOM matrix particle comprising Fraction C of Quillaja Saponaria Molina and not Fraction A of Quillaja Saponaria Molina.
HA tail association and head extension from the ISCOM matrix particle
The first recombinant influenza HA glycoprotein trimer has the HA glycoprotein tail associated with the first ISCOM matrix particle and the HA glycoprotein head extending distally from the first ISCOM matrix particle; the second recombinant influenza HA glycoprotein trimer has the HA glycoprotein tail associated with the second ISCOM matrix particle and the HA glycoprotein head extending distally from the second ISCOM matrix particle.
Type A influenza HA with transmembrane domain in each HaSMaN
Each of the first and the second HA glycoprotein is from a Type A influenza strain, and each contains a transmembrane domain.
HaSMaN preparation by combining HA-containing detergent core nanoparticle with Fraction A ISCOM matrix particle for at least about four hours
A method of preparing a HaSMaN comprising combining a detergent core nanoparticle containing hemagglutinin (HA) with an ISCOM matrix particle for at least about four hours, wherein the ISCOM matrix particle comprises Fraction A of Quillaja Saponaria Molina and not Fraction C of Quillaja Saponaria Molina, the HA contains a transmembrane domain, and the HA is from a Type A influenza strain.
HaSMaN preparation by combining HA-containing detergent core nanoparticle with Fraction C ISCOM matrix particle for at least about four hours
A method of preparing a HaSMaN comprising combining a detergent core nanoparticle containing hemagglutinin (HA) with an ISCOM matrix particle for at least about four hours, wherein the ISCOM matrix particle comprises Fraction C of Quillaja Saponaria Molina and not Fraction A of Quillaja Saponaria Molina, the HA contains a transmembrane domain, and the HA is from a Type A influenza strain.
The claim coverage is focused on HaSMaN-based influenza vaccine compositions and preparation methods defined by association of HA glycoprotein trimers with ISCOM matrix particles, mutual exclusivity of Quillaja Saponaria Molina saponin Fraction A versus Fraction C in the ISCOM matrix particle, use of Type A influenza HA containing a transmembrane domain, and HaSMaN preparation by combining HA-containing detergent core nanoparticles with the specified ISCOM matrix particle for at least about four hours.
Stated Advantages
Improved stability, including room-temperature storage.
Enhanced immune responses, including hemagglutination inhibition (HAI) titers versus commercial vaccines.
Comparable immunogenicity to bedside-mixed controls.
Thermal stability improvements dependent on HaSMaN formation.
Support for long shelf-life and simplified clinical logistics.
Documented Applications
Influenza vaccination via administration of the claimed composition to stimulate an immune response against influenza.
Use of intramuscular administration route for the method of stimulating an immune response against influenza.
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