Method for producing a vaccine composition that primes the human leukocyte antigen class I restriction CD8 T cell response to viral nonvirion membrane protein-derived epitopes.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- GENOVIE
- Filing Date
- 2026-03-18
- Publication Date
- 2026-06-23
AI Technical Summary
【0016】 1つの観点では、本発明は、ウイルス性病原体に対して使用するためのワクチン組成物を製造する方法であって、以下: a.対抗するワクチン組成物が望まれるウイルス病原体から、非ビリオン膜タンパク質由来のヒト白血球抗原クラスI制限エピトープ(非VIP由来HLAI-HRE)を同定すること; b.標的ウイルスに事前感染していないドナーから単離されたナイーブCD8 T細胞集団及び/又は標的ウイルスの活動性感染、潜在感染若しくは既往感染が確認されたドナーからのメモリーCD8 T細胞集団における、同定された非VIP由来HLAI-HREの免疫原性を分類すること; c.ナイーブドナーにおいて免疫原性が確認された非VIP由来HLAI-HRE又は標的ウイルスの活動性感染、潜在感染若しくは既往感染が確認されたドナーにおいてCD8 T細胞応答が観察された非VIP由来HLAI-HREを選択すること; d.選択された非VIP由来HLAI-HREをワクチン組成物に含めること を含む方法を提供する。
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Abstract
Claims
1. A method for producing a vaccine composition for use against a viral pathogen, the following: a. Identifying non-virion membrane protein-derived human leukocyte antigen class I restriction epitopes (non-VIP-derived HLAI-HREs) from viral pathogens for which a countermeasure vaccine composition is desired, using a combination of standardized donor vectors for HLA and antigen ORF constructs and genomic receptor sites in functionally genetically engineered immortal cell lines representing programmable eAPCs, where the eAPC is subsequently screened by a mass spectrometry (MS)-based method to identify HLA restriction antigens from ORFs integrated within a background of endogenous HLAI restriction repertoire derived from the eAPC protein itself, enabling systematic analysis of the ORF in a single HLA background (monoalerec); b. Classifying the immunogenicity of identified non-VIP-derived HLAI-HREs in naive CD8 T cell populations isolated from donors not prior to target virus infection and / or memory CD8 T cell populations from donors with confirmed active, latent, or past infection with the target virus; c. Select non-VIP-derived HLAI-HREs that have shown immunogenicity in naive donors, or non-VIP-derived HLAI-HREs that have shown a CD8 T cell response in donors with confirmed active, latent, or past infection with the target virus; d. Including selected non-VIP-derived HLAI-HRE in the vaccine composition. A method comprising the viral pathogen SARS-CoV-2.
2. The method according to claim 1, wherein multiple non-VIP-derived HLAI-HREs are selected to represent one or more HLAI-HREs among the HLAI alleles, which are alleles possessed by at least 60% of individuals in the target population for which the vaccine composition is designed, in order to be included in the vaccine composition.
3. The method according to claim 1 or 2, wherein one or more non-VIP-derived HLAI-HREs are selected to represent one or more HLAI-HREs among one or more HLAI alleles possessed by the individual under which the vaccine composition is designed, for inclusion in the vaccine composition.
4. The vaccine composition is as follows: a. Recombinant non-replicating or replicating viral vectors; b. Virus-like particles; c. Recombinant RNA constructs containing or not containing modified nucleotides; d. Recombinant DNA constructs that may or may not contain modified nucleotides; e. Recombinant proteins that contain or do not contain modified amino acids; f. Synthetic polypeptides containing or not containing modified amino acids The method according to any one of claims 1 to 3, comprising one or more vaccine vectors selected from.
5. The method according to claim 4, wherein one or more vaccine vectors are selected from a, b, or c, and the selected non-VIP-derived HLAI-HRE is incorporated into an expression construct that does not allow the expression of a functional non-VIP protein in host cells at the time of vaccine delivery, thereby inactivating the immune evasion activity of the viral non-VIP.
6. The following are the selected non-VIP originating HLAI-HRE offerings: a. Introducing point mutations and / or sequence insertions and / or sequence deletions within a full-length non-VIP ORF that inactivate protein function; b. Construction of synthetic nucleic acid sequences containing non-VIP ORF fragments encoding selected HLAI-HREs in the linked construct; c. The method of claim 5, provided by constructing one or more synthetic nucleic acid sequences comprising a non-VIP ORF fragment encoding a selected HLAI-HRE within a carrier protein sequence.
7. The method according to claim 4, wherein the one or more vaccine vectors are selected from d or e, the recombinant protein or synthetic polypeptide comprises one or more non-VIP derived HLAI-HREs, and the protein or polypeptide molecule comprises linked HLAI-HREs or encodes the HLAI-HREs within the carrier protein or polypeptide.
8. The method according to any one of claims 4 to 7, wherein one or more vaccine vectors further encode one or more B cell / immunoglobulin epitopes that prime a neutralizing Ig response.
9. The method according to any one of claims 4 to 8, wherein one or more vaccine vectors further encode one or more selected HLAII-HRE epitopes to prime a CD4 T cell response supporting B cell maturation and neutralizing antibody production, and / or to promote a non-VIP-derived HLAI-HRE-specific CD8 T cell response toward memory differentiation.
10. The method according to claim 8, wherein one or more B cell / immunoglobulin epitopes are modified to remove HLAI-HRE from VIP so as not to prime the CD8 T cell response to the VIP protein at vaccine delivery.
11. The method according to any one of claims 1 to 10, wherein step a of claim 1 further comprises genetically modified TCR-presenting cells (eTPCs).
12. The method according to any one of claims 1 to 11, wherein the selected non-VIP derived HLAI-HRE included in step d of claim 1 is included in preference to non-VIP HLAI-HRE from naive donors or donors in which a CD8 T cell response was observed in donors with confirmed active, latent, or past infection of the target virus.