Vaccine booster compositions for respiratory viral diseases

Inventors

KOK, Kin HangYuen, Kwok YungLAM, Joy Yan

Assignees

Centre for Virology Vaccinology and Therapeutics Ltd

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Publication Number

US-12102678-B2

Patent

Publication Date

2024-10-01

Expiration Date


Abstract

The present application provides chimeric proteins comprising comprising a receptor binding domain (“RBD”) of a SARS-CoV-2 spike protein (“S protein”) fused to a booster enhancer domain (“BED”) and uses thereof as vaccine or vaccine booster compositions. Also provided are method of boostering SARS-CoV-2 vaccines by administering to a vaccinated individual an effective amount of the vaccine booster composition, wherein the vaccine booster composition comprises a spike protein or a fragment thereof, and optionally wherein the vaccine booster composition is administered intranasally.

Core Innovation

The invention provides a chimeric protein comprising a receptor binding domain (RBD) of a SARS-CoV-2 spike protein (S protein) fused to a booster enhancer domain (BED). The BED comprises a fragment or a variant thereof of a nucleocapsid protein (N protein) of a coronavirus, and the BED enhances the booster function of the RBD.

The RBD comprises a fragment or a variant thereof of an S protein of the omicron variant of SARS-CoV-2 (SARS-CoV-2 lineage B.1.1.529). The invention further includes chimeric proteins that comprise the amino acid sequence of SEQ ID NO:4 or 5, or a variant thereof having at least 80% sequence homology to SEQ ID NO:4 or 5.

The invention also provides a method of enhancing the effect of a vaccine against SARS-CoV-2 in an individual who has been vaccinated. The method administers intranasally an effective amount of a vaccine booster composition comprising the chimeric protein, where the BED is derived from a fragment or a variant of a coronavirus nucleocapsid protein and enhances the booster function of the RBD.

Claims Coverage

The document presents three independent claim sets. Across these independent claims, the inventive features focus on an RBD-BED fusion architecture, BED derivation from a coronavirus nucleocapsid fragment or variant, Omicron-derived RBD content, specific sequence definitions and sequence homology thresholds, and intranasal administration to enhance the effect of an already-administered vaccine.

RBD fused to a booster enhancer domain (BED) that enhances booster function

A chimeric protein comprising a receptor binding domain (RBD) of a SARS-CoV-2 spike protein (S protein) fused to a booster enhancer domain (BED), wherein the BED comprises a fragment or a variant thereof of a nucleocapsid protein (N protein) of a coronavirus, and wherein the BED enhances the booster function of the RBD.

Omicron-derived RBD content in the RBD-BED chimeric protein

The chimeric protein wherein the RBD comprises a fragment or a variant thereof of an S protein of the omicron variant of SARS-CoV-2 (SARS-CoV-2 lineage B.1.1.529).

Sequence-defined RBD-BED chimeric protein with homology to SEQ ID NO:4 or 5

A chimeric protein comprising a receptor binding domain (RBD) of a SARS-CoV-2 spike protein (S protein) fused to a booster enhancer domain (BED), wherein the chimeric protein comprises the amino acid sequence of SEQ ID NO:4 or 5, or a variant thereof having at least 80% sequence homology to SEQ ID NO:4 or 5.

Intranasal vaccine boosting to enhance the effect of a vaccine in a vaccinated individual

A method of enhancing the effect of a vaccine against SARS-CoV-2 in an individual who has been vaccinated, comprising administering to the individual an effective amount of a vaccine booster composition, wherein the vaccine booster composition is administered intranasally and comprises a chimeric protein with an RBD fused to a BED derived from a coronavirus nucleocapsid protein fragment or variant.

Across the independent claim sets, the claimed concept is centered on an RBD-BED chimeric protein where the BED is derived from a coronavirus nucleocapsid fragment or variant and enhances the booster function of the RBD, including Omicron-derived RBD content, and on an intranasal method of administering a vaccine booster composition containing this chimeric protein to enhance the effect of a vaccine in a vaccinated individual.

Stated Advantages

Cost-effective production.

Stability.

Reduced invasiveness.

No infectious material handling.

Documented Applications

Preclinical mouse model vaccination and booster evaluation of nasal booster groups (N-RBDWT and N-RBDomicron) compared to PBS controls, with humoral response and neutralization measures against SARS-CoV-2 variants including Omicron.

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