Biology subjects

Yadav, R. T.

Publications and source records attributed to Yadav, R. T..

3 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↗

bioRxiv2025

Differential modulation of Interferon and Cell Death Responses defines Human vs Avian Influenza A Virus Strain-Specific Virulence and guides Combination Therapy.

Influenza A virus (IAV) poses a significant global health risk, with highly pathogenic strains like H5N1 (CFR [~]52%) causing severe disease compared to less lethal but more transmissible strains like H1N1 (CFR 0.01-0.03%). Although IAV primarily infects lung epithelial cells, causing cell death and tissue damage, the molecular basis of strain-specific pathogenesis remains poorly understood. Here we show that in cell culture, H5N1 induced more rapid and extensive cell death than H1N1. Since Interferon (IFN) signaling is key to innate immunity, we examined its role in virus-induced cell death using STAT1-knockout A549 cells and JAK/STAT pathway inhibitors like Baricitinib. Both approaches reduced cell death across various IAV strains, including H1N1, H5N1, H7N9, and H3N2. However, inhibition increased viral titers, raising concerns about its clinical use in isolation. To overcome this, we tested a combination of Oseltamivir (antiviral) and Baricitinib (anti-inflammatory). Post-infection treatment in a murine model reduced lung inflammation and improved survival. Given that both drugs are FDA-approved, this approach has strong translational potential for clinical IAV treatment.

microbiology↗

bioRxiv2022

A natural broad-spectrum inhibitor of enveloped virus entry, effective against SARS-CoV-2 and Influenza A Virus in preclinical animal models.

The COVID-19 pandemic has highlighted the need for novel antivirals for pandemic management and preparedness. Targeting host processes that are co-opted by viruses is an attractive strategy for developing antivirals with a high resistance barrier. Picolinic acid (PA) is a byproduct of tryptophan metabolism, endogenously produced in humans and other mammals. Here we report broad-spectrum antiviral effects of PA against enveloped viruses, including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), Influenza A virus (IAV), Flaviviruses, Herpes Simplex Virus, and Human Parainfluenza Virus. We further demonstrate using animal models that PA is effective against SARS-CoV-2 and IAV, especially as an oral prophylactic. The mode of action studies revealed that PA inhibits viral entry of enveloped viruses, primarily by interfering with viral-cellular membrane fusion, inhibiting virus-mediated syncytia formation, and dysregulating cellular endocytosis. Overall, our data establish PA as a broad-spectrum antiviral agent, with promising preclinical efficacy against pandemic viruses SARS-CoV-2 and IAV.

microbiology↗