Method of inducing immunity against SARS-CoV-2 using spike and nucleocapsid-ETSD immunogens delivered by RNA and replication-defective adenoviruses
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Publication Number
US-12285480-B2
Publication Date
2025-04-29
Expiration Date
Abstract
Disclosed herein are methods for inducing immunity against a severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV2) in a patient in need thereof. The method comprises administering a vaccine composition comprising a self-adjuvanted SARS-CoV2 Spike (S) RNA-based vaccine (AAHI-SC2), followed by administering a replication defective adenovirus (hAd5) vaccine composition, wherein the adenovirus comprises an E1 gene region deletion and an E2b gene region deletion.
Core Innovation
The document describes methods of inducing immunity against SARS-CoV-2 in a patient by administering a vaccine composition comprising a self-adjuvanted RNA-based vaccine in which the RNA encodes a SARS-CoV-2 spike (S) protein, and by administering a replication defective adenovirus (hAd5) vaccine composition. The hAd5 vaccine comprises an E1 gene region deletion and an E2b gene region deletion and includes a nucleotide encoding an S protein having the amino acid sequence of SEQ ID NO:6.
The hAd5 also comprises a chimeric protein that includes a SARS-CoV-2 nucleocapsid (N) protein and an endosomal targeting sequence (ETSD), wherein the chimeric protein has the amino acid sequence of SEQ ID NO:2. The chimeric N-ETSD construct is intended to localize the N antigen to endosomal/lysosomal compartments for immune processing, and the S antigen design is associated with enhanced cell-surface expression.
The document further describes heterologous prime-boost regimens combining the self-adjuvanted RNA-based vaccine with an adenovirus composition encoding N, including reported synergistic increases in variant-specific T-cell responses. Additional embodiments include recombinant yeast expressing N and/or S-fusion proteins, saliva-based immune monitoring, and oral or other mucosal administration.
Claims Coverage
The partial content provides one independent claim. The inventive coverage focuses on a heterologous prime-boost method using a self-adjuvanted RNA-based spike (S) vaccine together with a replication defective hAd5 vaccine containing specified E1/E2b deletions and specified antigen-encoding sequences (S and a chimeric N-ETSD construct).
Self-adjuvanted RNA-based SARS-CoV-2 spike vaccine prime
Administering a vaccine composition comprising a self-adjuvanted RNA-based vaccine, wherein the RNA encodes a SARS-CoV-2 spike (S) protein.
Replication defective hAd5 with E1 and E2b deletions encoding S and chimeric N-ETSD
Administering a replication defective adenovirus (hAd5) vaccine composition comprising an E1 gene region deletion and an E2b gene region deletion, and wherein the hAd5 comprises a nucleotide encoding a SARS-CoV-2 S protein having the amino acid sequence of SEQ ID NO:6 and a chimeric protein comprising a SARS-CoV-2 nucleocapsid (N) protein and an endosomal targeting sequence (ETSD), wherein the chimeric protein has the amino acid sequence of SEQ ID NO:2.
Overall, the claim coverage centers on inducing immunity by combining a self-adjuvanted RNA-based spike (S) administration with a replication defective hAd5 booster defined by E1 and E2b deletions and by encoding both a specified spike sequence (SEQ ID NO:6) and a chimeric nucleocapsid/endosomal targeting sequence (SEQ ID NO:2).
Stated Advantages
Induction of immunity against an antigen in a patient.
Enhanced cell-surface expression associated with the S antigen and endosomal/lysosomal localization of N-ETSD for MHC II presentation.
Induction of Th1-skewed humoral and CD4+/CD8+ T-cell responses.
Neutralization activity in vitro.
Synergistic increases in variant-specific T-cell responses in heterologous prime-boost regimens.
Immune monitoring to determine whether to administer a booster based on saliva analysis.
Documented Applications
Heterologous prime-boost vaccination to induce immunity against SARS-CoV-2 in a patient using an RNA-based spike vaccine and an hAd5 vaccine encoding S and N-ETSD.
Use of recombinant yeast expressing N and/or S-fusion proteins as additional embodiments for vaccine compositions.
Saliva-based immune monitoring and booster administration decision based on absence of SARS-CoV-2-targeting antibodies in saliva.
Oral or other mucosal administration and delivery route variations for the vaccine compositions.
Immune responses assessed including variant-specific T-cell responses for variants including B.1.351, B.1.1.7, P.1, and B.1.426.
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