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bioRxiv · 10.64898/2026.03.29.715080

Broad protection against Influenza A Viruses via an adjuvant-free mucosal microparticle vaccine with conserved CD8/CD4 bispecific peptides

Yadav, R. T.·Sharma, M.·Nagaraj, S. K.·Narayan, R.·Kaliappan, A.·Shanmugasundaram, U.·Chavan, R.·Rai, A. B.·Rai, R.·Keshav Prasad, T. S.·Sambhara, S.·Agarwal, R.·Tripathi, S.
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Abstract

Rapid antigenic evolution of Influenza A viruses (IAVs) enables their escape from strain-specific vaccine immunity and underscores 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 enable 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. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/715080v2_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@19fafedorg.highwire.dtl.DTLVardef@d73109org.highwire.dtl.DTLVardef@1d486edorg.highwire.dtl.DTLVardef@1e663c8_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Yadav, R. T., Sharma, M., Nagaraj, S. K., Narayan, R., Kaliappan, A., Shanmugasundaram, U., Chavan, R., Rai, A. B., Rai, R., Keshav Prasad, T. S., Sambhara, S., Agarwal, R., Tripathi, S.. 2026-03-31. Broad protection against Influenza A Viruses via an adjuvant-free mucosal microparticle vaccine with conserved CD8/CD4 bispecific peptides. https://doi.org/10.64898/2026.03.29.715080

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