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Antigen anisotropy: The overlooked geometric determinant of vaccine immunogenicity and fidelity
10.1080/21645515.2026.2638640
2026-03-04
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Abstract
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Antigen anisotropy, the directional dependence of protein conformation, epitope exposure, and conformational dynamics, is an under-appreciated determinant of vaccine immunogenicity. Preserving this geometric fidelity may influence outcomes such as neutralization breadth, affinity maturation, and B/T-cell response quality. Native antigens engage B-cell receptors, T-cell receptors, and MHC through oriented interactions that rely on spatial and dynamic constraints for effective immune recognition. This framework is increasingly relevant amid widespread use of nucleoside-modified mRNA vaccines, as recent studies suggest platform-specific deviations in antigen geometry and processing. Platform interventions including chemical inactivation (e.g., formaldehyde and β-propiolactone), formulation and storage conditions, and mRNA design choices (e.g., N1-methylpseudouridine incorporation, codon optimization) can introduce perturbations that influence folding, glycan shielding, epitope presentation, and hydrodynamic behavior. These effects can generate antigen ensembles that diverge from native forms, and may plausibly contribute to differences in response breadth and quality. Prioritizing anisotropy preservation offers a complementary design principle for next generation vaccines, one that seeks to more closely recapitulate the geometric and dynamic features of natural infection and may improve the predictability and durability of protective immunity.
Keywords:
Antigen anisotropy
vaccine immunogenicity
N1-methylpseudouridine
protein conformation
epitope presentation
conformational dynamics
mRNA vaccines
glycosylation
immune fidelity
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Papers: 6
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Daniel Santiago
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4
Papers: 97
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independent researcher
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732
Papers: 652
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