Prophylactic efficacy against Mycobacterium tuberculosis using ID93 and lipid-based adjuvant formulations in the mouse model.

An estimated 10 million people developed tuberculosis (TB) disease in 2019 which underscores the need for a vaccine that prevents disease and reduces transmission. The aim of our current studies is to characterize and test a prophylactic tuberculosis vaccine comprised of ID93, a polyprotein fusion antigen, and a liposomal formulation [including a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant, GLA) and QS-21] in a preclinical mouse model of TB disease. Comparisons of the ID93+GLA-LSQ vaccines are also made to the highly characterized ID93+GLA-SE oil-in-water emulsion adjuvant, which are also included these studies.

Controlled Covalent Conjugation of a Tuberculosis Subunit Antigen (ID93) to Liposome Improved Th1-Type Cytokine Recall Responses in Human Whole Blood.

Tuberculosis (TB) remains a foremost poverty-related disease with a high rate of mortality despite global immunization with Bacille Calmette-Guérin (BCG). Several adjuvanted recombinant proteins are in clinical development for TB to protect against the disease in infants and adults. Nevertheless, simple mixing of adjuvants with antigens may not be optimal for enhancing the immune response due to poor association.

A Nanostructured Lipid Carrier for Delivery of a Replicating Viral RNA Provides Single, Low-Dose Protection against Zika.

Since the first demonstration of in vivo gene expression from an injected RNA molecule almost two decades ago, the field of RNA-based therapeutics is now taking significant strides, with many cancer and infectious disease targets entering clinical trials. Critical to this success has been advances in the knowledge and application of delivery formulations. Currently, various lipid nanoparticle (LNP) platforms are at the forefront, but the encapsulation approach underpinning LNP formulations offsets the synthetic and rapid-response nature of RNA vaccines.

Modulating potency: Physicochemical characteristics are a determining factor of TLR4-agonist nanosuspension activity.

Activity of adjuvanted vaccines is difficult to predict in vitro and in vivo. The wide compositional and conformational range of formulated adjuvants, from aluminum salts to oil-in-water emulsions, makes comparisons between physicochemical and immunological properties difficult. Even within a formulated adjuvant class, excipient selection and concentration can alter potency and physicochemical properties of the mixture.

Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.

Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR) 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA). We assessed the effects of GLA on murine and human dendritic cells (DC) by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses.

Lateral flow immunoassay for diagnosis of Trypanosoma cruzi infection with high correlation to the radioimmunoprecipitation assay.

The incidence of blood donors seropositive for Trypanosoma cruzi in North America has increased with population migration and more rigorous surveillance. The United States, considered nonendemic for T. cruzi, could therefore be at risk to exposure to parasite transmission through blood or organ donations.