Biology subjects

Gunasena, M.

Publications and source records attributed to Gunasena, M..

3 recordsLinked to original sources

bioRxiv2024

BCG immunization-induced KLRG1+ NK cells show memory-like responses to mycobacterial and HIV antigens

The live-attenuated Bacille-Calmette-Guerin (BCG) vaccine is the only approved vaccine against Mycobacterium tuberculosis (MTB), offering broad protection against tuberculosis (TB) and other infectious diseases. Trained immunity, a process where innate immune cells develop memory-like features, is considered one of the BCG vaccines protective mechanisms. In this study, we investigated the effect of BCG vaccination on Natural Killer (NK) cells, a key subset of the innate immune system, and their ability to give rise to heterologous memory-like responses to HIV antigens. Here we found that BCG vaccine-induced KLRG1+ NK cells exhibit memory-like responses to both MTB and HIV antigens, as evidenced by their increased production of IFN{gamma} upon exposure to MTB and HIV-gag antigens. This finding is of great importance, as co-infection with HIV and TB is highly relevant in Asia and Africa where BCG is administered. Understanding these responses is crucial for the development of more effective vaccines and therapeutics for both TB and HIV.

immunology↗

bioRxiv2024

Novel Oral Adjuvant to Enhance Cytotoxic Memory-Like NK Cell Responses in an HIV Vaccine Platform

Antibody-dependent cell-mediated cytotoxicity, mediated by natural killer (NK) cells and antibodies, emerged as a secondary correlate of protection in the RV144 HIV vaccine clinical trial, the only vaccine thus far demonstrating some efficacy in human. Therefore, leveraging NK cells with enhanced cytotoxic effector responses may bolster vaccine induced protection against HIV. Here, we investigated the effect of orally administering indole-3-carbinol (I3C), an aryl hydrocarbon receptor (AHR) agonist, as an adjuvant to an RV144-like vaccine platform in a mouse model. We demonstrate the expansion of KLRG1-expressing NK cells induced by the vaccine together with I3C. This NK cell subset exhibited enhanced vaccine antigen-specific cytotoxic memory-like features. Our study underscores the potential of incorporating I3C as an oral adjuvant to HIV vaccine platforms to enhance antigen-specific (memory-like) cytotoxicity of NK cells against HIV-infected cells. This approach may contribute to enhancing the protective efficacy of HIV preventive vaccines against HIV acquisition.

immunology↗

bioRxiv2023

Unveiling the Immune Dynamics of Neisseria Persistent Oral Colonization: A Roadmap for Innovative Vaccine Strategies

Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus Neisseria, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans perspective, but lacks models that study immune responses in the context of long-term persistence. Neisseria musculi, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to Neisseria musculi colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from lung, blood and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic Neisseria. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/572139v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1728fdaorg.highwire.dtl.DTLVardef@426a5forg.highwire.dtl.DTLVardef@55a90forg.highwire.dtl.DTLVardef@1ce3ff6_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗