Antigen Format Determines Immunogenicity of AAV-Based SARS-CoV-2 Vaccines: Full-Length Spike Versus Truncated Subunits.

ABSTRACT:

Background

Antigen format strongly influences the immunogenicity of gene-based vaccines. Full-length Spike is widely used in licensed COVID-19 vaccines, while truncated subunits such as S1 or the receptor-binding domain (RBD) may simplify vector design but risk reduced potency. We aimed to compare these antigen formats in an AAV9 delivery platform.

Methods

BALB/c mice were immunized intramuscularly with recombinant AAV9 encoding full-length Spike, S1, or RBD at doses of 1 × 10¹⁰ or 1 × 10¹¹ viral genomes. Immune responses were assessed by serology, virus neutralization, T-cell profiling, and histopathology.

Results

All constructs expressed antigen in vitro and in vivo. Only full-length Spike elicited robust neutralizing antibodies at both doses,

SUBMITTER: Vakhrusheva AV 

PROVIDER: S-EPMC12737442 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature