Abstract
Rapid antigenic evolution of Influenza A viruses (IAVs) enables their escape from strain-specific vaccine immunity, underscoring the need for broadly protective strategies. Here, we describe a modular, adjuvant-free mucosal vaccine platform that elicits potent and cross-protective T cell immunity. The approach uses overlapping CD4+ and CD8+ epitope-dense regions from the consensus IAV M1 and NP proteins, identified through computational and functional screening. These peptides are delivered using polylactic-co-glycolic acid (PLGA) microparticles, engineered for selective uptake by antigen-presenting cells and enabling sustained, pH-responsive antigen release. This design enhances antigen processing and MHC cross-presentation, functionally substituting for a conventional adjuvant. This formulation drives robust activation of primed human as well as murine CD4+ and CD8+ T cells and confers broad protection against homologous (H1N1, H3N2) as well as heterologous (H5N1) IAV strains in immunized mice. Overall, this adjuvant-free dose-sparing platform establishes an adaptable framework for next-generation broadly-protective vaccines against rapidly evolving viruses.
Competing Interest Statement
R.T.Y. and S.T. are co-inventors on an unpublished patent titled Immunogenic peptide(s), composition(s) and application(s) thereof broadly protective against Influenza, Indian patent application number 202541082426. The other authors declare that they have no competing interests.
Funder Information Declared
DBT-ENDFLU, BT/IN/EU-INF/15/RV/19-20
Source:
Link: https://www.biorxiv.org/content/10.64898/2026.03.29.715080v2
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