The in silico prediction of bacterial surface exposed proteins is of growing interest for the rational development of vaccines and in the study of bacteria-host relationships, whether pathogenic or host beneficial. This interest is driven by the increase in the use of DNA sequencing as a major tool in the early characterization of pathogenic bacteria and, more recently, even of complex ecosystems at the host-environment interface in metagenomics approaches. Current protein localization protocols are not suited to this prediction task as they ignore the potential surface exposition of many membrane-associated proteins. Therefore, we developed a new flow scheme, SurfG+, for the processing of protein sequence data with the particular aim of identification of potentially surface exposed (PSE) proteins from Gram-positive bacteria, which was validated for Streptococcus pyogenes. The results of an exploratory case study on closely related lactobacilli of the acidophilus group suggest that the yogurt bacterium Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) dedicates a relatively important fraction of its coding capacity to secreted proteins, while the probiotic gastrointestinal (GI) tract bacteria L. johnsonii and L. gasseri appear to encode a larger variety of PSE proteins, that may play a role in the interaction with the host.

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2.

Chemokines control the migration of a large array of cells by binding to specific receptors on cell surfaces. The biological function of chemokines also depends on interactions between nonreceptor binding domains and proteoglycans, which mediate chemokine immobilization on cellular or extracellular surfaces and formation of fixed gradients. Chemokine gradients regulate synchronous cell motility and integrin-dependent cell adhesion. Of the various chemokines, CXCL12 has a unique structure because its receptorbinding domain is distinct and does not overlap with the immobilization domains. Although CXCL12 is known to be essential for the germinal center (GC) response, the role of its immobilization in biological functions has never been addressed. In this work, we investigated the unexplored paradigm of CXCL12 immobilization during the germinal center reaction, a fundamental process where cellular traffic is crucial for the quality of humoral immune responses. We show that the structure of murine germinal centers and the localization of GC B cells are impaired when CXCL12 is unable to bind to cellular or extracellular surfaces. In such mice, B cells carry fewer somatic mutations in Ig genes and are impaired in affinity maturation. Therefore, immobilization of CXCL12 is necessary for proper trafficking of B cells during GC reaction and for optimal humoral immune responses.CXCL12 | humoral immune responses | germinal center reaction C hemokines control the migration of a large array of cells and, as a consequence, regulate cell function and homeostasis in many tissues (1). In particular, they regulate the migration and positioning of lymphocytes in secondary lymphoid organs (2). Besides specific signaling delivered by engagement of specific receptors on cell surfaces, the function of chemokines also depends on interactions between nonreceptor binding domains and the glycanicglycosaminoglycan (GAG) moiety of proteoglycan, particularly heparan sulfate (HS), of the extracellular matrix and cell surfaces (3). This interaction results in immobilization of chemokines and allows the formation of fixed local gradients that, in in vitro models, regulate the synchronous coordination of cell motility (haptotaxis) and integrin-dependent cell adhesion (2). An immobilized, but not free, chemokine is a hallmark of cell signaling (4).The importance of chemokine immobilization for their function has not been fully addressed, and its relevance has been difficult to evaluate in vivo, given the lack of information on the structure-function relationship of chemokine/HS interactions.Of the various chemokines, C-X-C motif chemokine 12 (CXCL12) [also known as stromal-cell-derived factor 1 (SDF-1)] has unique structural characteristics because its binding domains, to the receptor C-X-C chemokine receptor type 4 (CXCR4) and to HS, are distinct and nonoverlapping, permitting the separation of their respective functions (5, 6). The interaction with proteoglycans is believed to contribute to CXCL12 activity by enabling the formation of local gra...