Publications by authors named "Gayathri Sam"

Polyhydroxybutyrate (PHB) is a biodegradable and biocompatible biopolyester, naturally produced and self-assembled as spherical inclusions inside bacteria. These PHB particles contain a hydrophobic PHB core covalently coated with PHB synthase (PhaC), which serves as an anchoring linker for foreign proteins of interest. Protein engineering of PhaC enables the display of biologically active protein functions on the surface of PHB particles suitable for different applications.

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Coxiella burnetti is an intracellular bacterium that causes Q fever, a disease of worldwide importance. Q-VAX , the approved human Q fever vaccine, is a whole cell vaccine associated with safety concerns. Here a safe particulate subunit vaccine candidate is developed that is ambient-temperature stable and can be cost-effectively manufactured.

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Q fever is an infectious zoonotic disease, caused by the Gram-negative bacterium Coxiella burnetii. Transmission occurs from livestock to humans through inhalation of a survival form of the bacterium, the Small Cell Variant, often via handling of animal parturition products. Q fever manifests as an acute self-limiting febrile illness or as a chronic disease with complications such as vasculitis and endocarditis.

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Group A Streptococcus (Strep A) is a life-threatening human pathogen with no licensed vaccine. Here, we used a biopolymer particle (BP) approach to display repeats of Strep A vaccine candidate peptides p*17 and K4S2 derived from M and non-M protein, respectively. BPs densely displaying both peptides (BP-p*17-S2) were successfully assembled in one-step inside an engineered endotoxin-free Escherichia coli strain.

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Vaccines remain the best approach for the prevention of infectious diseases. Protein subunit vaccines are safe compared to live-attenuated whole cell vaccines but often show reduced immunogenicity. Subunit vaccines in particulate format show improved vaccine efficacy by inducing strong immune responses leading to protective immunity against the respective pathogens.

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Immunogenic carrier proteins such as the non-toxic diphtheria toxin variant, cross-reacting material 197 (CRM197), are widely used in subunit vaccine formulations to boost immunogenicity of chemically conjugated antigens. Conjugate vaccines are inherently expensive due to laborious manufacturing steps. Here, this work develops a particulate vaccine platform based on using engineered Escherichia coli to assemble CRM197-antigen fusion proteins into discrete submicron-sized particles.

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