Biology subjects

Sathkumara, H.

Publications and source records attributed to Sathkumara, H..

3 recordsLinked to original sources

bioRxiv2026

Malnourishment and expanded microbiome maintain superior efficacy of the recombinant tuberculosis vaccine BCG::ESAT-6-PE25SS

Tuberculosis (TB) remains the leading cause of infectious mortality. The limited efficacy of the only TB vaccine, Bacille Calmette-Guerin (BCG) against pulmonary disease necessitates improved vaccines. Host factors such as malnutrition and microbiome composition shape immune responses in humans, though these factors are overlooked in preclinical vaccine evaluation. Here we show that a recombinant BCG strain, BCG::ESAT-6-PE25SS, confers superior protection compared to BCG across murine models of malnutrition, antibiotic-induced dysbiosis and environmentally enriched microbiota. Unexpectedly, malnourished mice displayed reduced Mycobacterium tuberculosis (Mtb) burden, associated with altered host metabolism and immune composition. Microbiome disruption increased TB susceptibility, whereas diversification of microbiota enhanced resistance and immune heterogeneity. Vaccine efficacy correlated with enrichment of known immunomodulatory microbial taxa. These findings suggest diet-microbiome-immunity interactions as potential key determinants of TB pathogenesis and provide evidence for the importance of vaccine candidate evaluation under physiologically relevant co-morbid conditions

microbiology↗

bioRxiv2024

A modular self-assembling and self-adjuvanting multiepitope peptide nanoparticle vaccine platform to improve the efficacy and immunogenicity of BCG

After more than a century since its initial development, Bacille Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Subunit boosters are considered a viable strategy to enhance BCG efficacy, which often wanes in adolescence. While many studies on booster subunit vaccines have concentrated on recombinant proteins, here we developed a novel modular peptide-based subunit vaccine platform that is flexible, cold-chain independent and customizable to diverse circumstances and populations. Each individual peptide building block consists of a linear arrangement comprising a 15-leucine self-assembly inducer moiety, a Mycobacterium tuberculosis (Mtb) target epitope and an HLA-E binding moiety, with each moiety separated by a triple lysine spacer. The building blocks, in any combination, were able to form a multiepitope nanoparticle. Six Mtb epitopes were selected to produce the self-assembling and self-adjuvanting peptide-based TB nano-vaccine candidate PNx6. In vivo vaccination-challenge experiments demonstrated that subcutaneous boost of parenteral BCG immunization with PNx6 significantly enhanced its immunogenicity and improved its protective efficacy in a murine model of TB by more than 5-fold. Our study present evidence that purely amphiphilic peptides self-assemble into self-adjuvanting nanoparticles with appropriate size and morphology for TB vaccination with great potential for a multitude of other diseases.

microbiology↗

bioRxiv2020

Disparate effects of metformin on Mycobacterium tuberculosis infection in diabetic and non-diabetic mice

Comorbid type 2 diabetes poses a great challenge to the global control of tuberculosis. Here we assessed the efficacy of metformin (MET); an anti-diabetic drug, in mice infected with a very-low dose of Mycobacterium tuberculosis. In contrast to diabetic mice, infected non-diabetic mice that received the same therapeutic concentration of MET presented with significantly higher disease burden. This warrants further studies to investigate the disparate efficacy of MET against tuberculosis in diabetic and non-diabetic individuals.

microbiology↗