PROJECT HELIX-HTT | Huntington’s-Adjacent Neuro-Oncology Vaccine Program | Validated Antigen Master Inventory

DV-01 — Validated Antigen Master Inventory

PROJECT HELIX-HTT | Huntington’s-Adjacent Neuro-Oncology Vaccine Program

Phase: II — Preclinical Vaccine Development

Module: 1 — Antigen Validation Program

Document Code: SCF-DV01-VAMI-NO-0001

Purpose: Confirm which candidate antigens are suitable for vaccine construct engineering.

1. Inventory Purpose

The Validated Antigen Master Inventory is the controlled list of vaccine candidate antigens that have passed the first preclinical validation layer.

An antigen is advanced only if it demonstrates:

Requirement	Meaning
Expression	The tumor produces the antigen source
Presentation	The peptide is displayed by HLA/MHC
Immunogenic potential	T cells can plausibly recognize it
Stability	The antigen is not rapidly lost
Safety	Low predicted CNS cross-reactivity

2. Antigen Validation Categories

Class	Antigen Type	Development Role
VAMI-A	Personalized neoantigens	Primary vaccine backbone
VAMI-B	Fusion-derived antigens	High-priority tumor-specific targets
VAMI-C	Tumor-associated antigens	Breadth and redundancy
VAMI-D	Alternative splice antigens	Tumor-adaptive targets
VAMI-E	SCF experimental stress antigens	Research-only exploratory layer

3. Master Validated Antigen Inventory Table

Antigen ID	Class	Source Evidence	Expression	Presentation	Stability	CNS Safety	Decision
VAMI-001	Neoantigen	MCAT + EXAT + HCM + PAL	High	Confirmed	Persistent	Green	Advance
VAMI-002	Neoantigen	MCAT + EXAT + HCM + PAL	High	Confirmed	Persistent	Green	Advance
VAMI-003	Fusion	MCAT + EXAT + HCM + PAL	Moderate–High	Confirmed	Persistent	Green	Advance
VAMI-004	Neoantigen	MCAT + EXAT + HCM	High	Predicted	Variable	Green	Backup
VAMI-005	TAA	EXAT + HCM + PAL	High	Confirmed	Persistent	Yellow	Backup
VAMI-006	Splice Antigen	EXAT + HCM	Moderate	Predicted	Variable	Green	Exploratory
VAMI-007	SCF Stress Antigen	EXAT + MES + PAL	Moderate	Confirmed	Variable	Yellow	Research-only

4. Validation Score

VAMI Score =
Expression Strength
+ Presentation Confidence
+ Immunogenic Potential
+ Antigen Stability
+ Tumor Specificity
- CNS Cross-Reactivity Risk
- Immune Escape Risk

Score Range	Validation Class	Action
≥85	Validated Primary	Advance to construct design
70–84	Validated Backup	Reserve / backup antigen
55–69	Exploratory	Research-only
<55	Rejected	Exclude

5. Primary Antigen Set

Recommended for vaccine construct engineering:

Slot	Antigen Class	Role
A1	Neoantigen	Core tumor-specific target
A2	Neoantigen	Core tumor-specific target
A3	Fusion antigen	High-specificity tumor junction target
A4	Neoantigen	Backup clonal target
A5	TAA	Breadth support

Primary vaccine composition goal:

60–70% personalized neoantigens, 10–20% fusion antigens, 10–20% tumor-associated antigens.

6. Backup Antigen Set

Antigen ID	Reason for Backup Status
VAMI-004	Predicted presentation only; needs immunopeptidomics confirmation
VAMI-005	CNS safety yellow flag; requires additional cross-reactivity review
VAMI-006	Alternative splice antigen; requires stronger persistence data

7. SCF Experimental Stress Antigen Set

Antigen ID	Experimental Rationale	Use Status
VAMI-007	May reflect DNA-repair stress / hypoxia-adaptive tumor state	Research-only

These antigens are not included in first-generation clinical vaccine constructs until additional safety and immunogenicity evidence is available.

8. Validation Evidence Requirements

Evidence Layer	Required for Primary Advancement?
Mutation Catalog	Yes for neoantigens
Expression Atlas	Yes
HLA Compatibility Matrix	Yes
Presented Antigen Library	Strongly preferred
SCF Microenvironment Report	Yes
CNS Safety Review	Mandatory
Immune Escape Review	Mandatory

9. Go / No-Go Decision Rules

Advance Antigen If:

Expression is moderate or high
HLA presentation is confirmed or strongly predicted
CNS safety is green
Immune escape risk is low or manageable
Antigen supports vaccine breadth

Hold / Backup If:

Presentation is predicted but not confirmed
CNS safety is yellow
Stability is variable

Exclude If:

High normal CNS similarity
Poor expression
No presentation evidence
High immune escape risk
Severe neuroimmune safety concern

10. Deliverable Output Files

Output	Description
VAMI-01	Primary validated antigen list
VAMI-02	Backup antigen list
VAMI-03	Experimental SCF antigen list
VAMI-04	CNS safety review table
VAMI-05	Immune escape risk table
VAMI-06	Construct-readiness summary

11. Decision Gate

Advance to Module 2 — Vaccine Construct Engineering if:

At least 8 primary/backup antigens are available
At least 3 antigens have confirmed presentation
CNS safety review is acceptable
No dominant immune escape risk is detected
SCF-MES is MES-A or MES-B, or MES-C with correctable barriers

Status

DV-01 Status: Complete

Phase II Next Deliverable: DV-02 — Vaccine Construct Engineering Package