Vaccine Conjugates
Constructive.bio produces vaccine conjugates with defined antigen-to-carrier ratios through site-specific ncAA-mediated bio-orthogonal chemistry. Unlike conventional random conjugation — which yields heterogeneous mixtures with variable antigen loading, batch inconsistency, and epitope masking — our approach delivers homogeneous conjugates with predictable immunogenicity and reproducible manufacturing.
The Problem
Conjugate vaccines link polysaccharide or peptide antigens to carrier proteins to elicit robust immune responses. Current manufacturing relies on random chemical conjugation to lysine or cysteine residues, producing heterogeneous mixtures with variable antigen-to-carrier ratios (typically 2–15 antigens per carrier). This heterogeneity causes batch-to-batch variability in immunogenicity, complicates quality control, and can mask critical epitopes on both antigen and carrier, reducing vaccine efficacy.
Our Approach
Constructive.bio incorporates ncAAs bearing bio-orthogonal reactive handles — azide or tetrazine groups — at genetically defined positions on the carrier protein. These handles react selectively with complementary groups on the antigen via click chemistry (SPAAC or inverse electron-demand Diels-Alder), achieving conjugation at exact sites with no off-target modification. By controlling the number and position of ncAA incorporation sites, we produce conjugates with defined antigen loading ratios and preserved epitope accessibility on both components.
Key Capabilities
Defined antigen-to-carrier ratios through site-specific ncAA placement — no random conjugation
Preserved epitope accessibility on both antigen and carrier protein
Bio-orthogonal click chemistry conjugation compatible with multiple antigen types
Batch-to-batch consistency enabling streamlined quality control and regulatory filing