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Demberg, T.

Publications and source records attributed to Demberg, T..

2 recordsLinked to original sources

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↗

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↗