Biology subjects

Shanmugasundaram, U.

Publications and source records attributed to Shanmugasundaram, U..

2 recordsLinked to original sources

bioRxiv2026

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

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

bioengineering↗

bioRxiv2020

Control of Mycobacterium tuberculosis Infection in Lungs is Associated with Recruitment of Antigen-Specific Th1 and Th17 cells Co-expressing CXCR3 and CCR6.

Mycobacterium tuberculosis (Mtb)-specific T cell responses associated with immune control during asymptomatic latent tuberculosis infection (LTBI) remain poorly understood. Using a non-human primate (NHP) aerosol model, we studied the kinetics, phenotypes and functions of Mtb antigen-specific T cells in peripheral and lung compartments of Mtb-infected asymptomatic rhesus macaques by longitudinally sampling blood and bronchoalveolar lavage (BAL), for up to 24 weeks post-infection. We found significantly higher frequencies of Mtb-specific effector and memory CD4 and CD8 T cells producing IFN-{gamma} in the airways compared to peripheral blood, which were maintained throughout the study period. Moreover, Mtb-specific IL-17+ and IL-17/IFN-{gamma} double-positive T cells were present in the airways but were largely absent in the periphery, suggesting that balanced mucosal Th1/Th17 responses are associated with LTBI. The majority of Mtb-specific CD4 T cells that homed to the airways expressed the chemokine receptor CXCR3 and co-expressed CCR6. Notably, CXCR3+CD4+ cells were found in granulomatous and non-granulomatous regions of the lung and inversely correlated with Mtb burden. Our findings provide novel insights into antigen-specific T cell responses associated with asymptomatic Mtb infection that are relevant for developing better strategies to control TB.

immunology↗