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Biology subjects

Wagner, R.

Publications and source records attributed to Wagner, R..

2 recordsLinked to original sources

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

Effective and safe vaccines against SARS-CoV-2 are highly desirable to prevent casualties and societal cost caused by Covid-19 pandemic. The receptor binding domain (RBD) of the surface-exposed spike protein of SARS-CoV-2 represents a suitable target for the induction of neutralizing antibodies upon vaccination. Small protein antigens typically induce weak immune response while particles measuring tens of nanometers are efficiently presented to B cell follicles and subsequently to follicular germinal center B cells in draining lymph nodes, where B cell proliferation and affinity maturation occurs. Here we prepared and analyzed the response to several DNA vaccines based on genetic fusions of RBD to four different scaffolding domains, namely to the foldon peptide, ferritin, lumazine synthase and {beta}-annulus peptide, presenting from 6 to 60 copies of the RBD on each particle. Scaffolding strongly augmented the immune response with production of neutralizing antibodies and T cell response including cytotoxic lymphocytes in mice upon immunization with DNA plasmids. The most potent response was observed for the 24-residue {beta}-annulus peptide scaffold that forms large soluble assemblies, that has the advantage of low immunogenicity in comparison to larger scaffolds. Our results support the advancement of this vaccine platform towards clinical trials.

immunology

Short- and long-read metagenomics of South African gut microbiomes reveal a transitional composition and novel taxa

Human gut microbiome research focuses on populations living in high-income countries or on the other end of the spectrum, namely non-urban agriculturalist and hunter-gatherer societies. The scarcity of research between these extremes limits our understanding of how the gut microbiota relates to health and disease in the majority of the worlds population. We present the first study evaluating gut microbiome composition in transitioning South African populations using short- and long-read sequencing. We analyzed stool samples from adult females (age 40 - 72) living in rural Bushbuckridge municipality (n=118) or urban Soweto (n=51) and find that these microbiomes are taxonomically intermediate between those of individuals living in high-income countries and traditional communities. We demonstrate that reference collections are incomplete for characterization of microbiomes of individuals living outside high-income countries, resulting in artificially low species-level beta diversity measurements. To improve reference databases, we generated complete genomes of undescribed taxa, including Treponema, Lentisphaerae, and Succinatimonas species. Our results suggest that the gut microbiome in South African populations do not exist along a simple "western-nonwestern" axis and that these populations contain microbial diversity that remains to be described.

genomics