Group A Streptococcus (GAS) infection causes a range of lifethreatening diseases, including rheumatic heart disease. Cyclic peptides offer an attractive solution for presentation of short peptide antigens due to their stability and structurally constrained conformation. We investigated a cyclic carrier decapeptide incorporating a B cell GAS peptide epitope, a universal T helper epitope, and a synthetic toll-like receptor 2-targeting moiety as a possible self-adjuvanting GAS vaccine. A structure−activity relationship of the cyclic lipopeptide vaccine showed successful induction of J8-specific systemic immunoglobulin G (IgG) antibodies when administered subcutaneously without an additional adjuvant. Interestingly, the physical mixture control induced the highest titers of all vaccine compounds, with antibodies from mice immunized with this physical mixture control shown to effectively opsonize multiple strains of clinically isolated GAS bacteria. This study showed the capability for a self-adjuvanting cyclic delivery system to act as a vehicle for the delivery of GAS peptide antigens to treat GAS infections.
Male and female human subjects show contrasting propensities to misuse drugs of addiction, including alcohol. These differences lead to different psychological and neurological consequences, such as the likelihood of developing dependence. The pattern and extent of brain damage in alcohol‐use disorder cases also varies with comorbid disease. To explore mechanisms that might underlie these outcomes, we used autopsy tissue to determine mRNA transcript expression in relation to genotype for two GABAA receptor subunit genes. We used quantitative Real‐Time PCR to measure GABRA6 and GABRA2 mRNA concentrations in dorsolateral prefrontal and primary motor cortices of alcohol‐use disorder subjects and controls of both sexes with and without liver disease who had been genotyped for these GABAA receptor subunit genes. Cirrhotic alcohol‐use disorder cases had significantly higher expression of GABRA6 and GABRA2 transcripts than either controls or non‐cirrhotic alcohol‐use disorder cases. Differences were observed between sexes, genotypes and brain regions. We show that sex differences in subjects with GABRA6 and GABRA2 variants may contribute to differences in susceptibility to alcohol‐use disorder and alcohol‐induced cirrhosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.