Outer Membrane Vesicles as a Versatile Platform for Vaccine Development: Engineering Strategies, Applications and Challenges.

Outer membrane vesicles (OMVs) are nanosized vesicles naturally secreted by Gram-negative bacteria and represent a promising platform for vaccine development. OMVs possess inherent immunostimulatory properties due to the presence of pathogen-associated molecular patterns (PAMPs), providing self-adjuvanting capabilities and the ability to elicit both innate and adaptive immune responses. This review outlines the advantages of OMVs over traditional vaccine strategies, including their safety, modularity, and the potential for genetic engineering to enable targeted antigen delivery.

Intranasal spike and nucleoprotein fusion protein-based vaccine provides cross-protection and reduced transmission against SARS-CoV-2 variants.

The effectiveness of intramuscular vaccines aimed at preventing severe COVID-19 remains limited due to waning immunity and the emergence of novel variants. Next-generation vaccines are needed for broader protection and blocking virus transmission. Here, we rationally designed an original nasal subunit vaccine composed of a fusion protein (SwFN) made of Wuhan spike and nucleoprotein combined with biocompatible mucosal nanocarriers (Nc).

Nasal administration of recombinant secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung.

Background: Metastases are the leading cause of mortality in many cancer types and lungs are one of the most common sites of metastasis alongside the liver, brain, and bones. In melanoma, 85% of late-stage patients harbor lung metastases. A local administration could enhance the targeting of metastases while limiting the systemic cytotoxicity.

a new class of biopharmaceuticals in the therapeutic arsenal against cancer.

Background: Microorganisms that can be used for their lytic activity against tumor cells as well as inducing or reactivating antitumor immune responses are a relevant part of the available immunotherapy strategies. Viruses, bacteria and even protozoa have been largely explored with success as effective human antitumor agents. To date, only one oncolytic virus-T-VEC-has been approved by the US Food and Drug Administration for use in biological cancer therapy in clinical trials.

CR3 Engaged by PGL-I Triggers Syk-Calcineurin-NFATc to Rewire the Innate Immune Response in Leprosy.

, the causative agent of leprosy, is unique amongst human pathogens in its capacity to produce the virulence factor phenolic glycolipid (PGL)-I. In addition to mediating bacterial tropism for neurons, PGL-I interacts with Complement Receptor (CR)3 on macrophages (MPs) to promote infection. We demonstrate here that PGL-I binding to CR3 also enhances bacterial invasion of both polymorphonuclear neutrophils (PMNs) and dendritic cells (DCs).

The C3HeB/FeJ mouse model recapitulates the hallmark of bovine tuberculosis lung lesions following Mycobacterium bovis aerogenous infection.

Achieving the control of bovine tuberculosis (bTB) would require the discovery of an efficient combined immunodiagnostic and vaccine strategy. Since in vivo experiments on cattle are not ethically and economically acceptable there is a need for a cost-effective animal model capable of reproducing, as closely as possible, the physiopathology of bTB to (i) better characterize the cellular and molecular features of bTB immunopathogenesis and (ii) screen preclinical vaccine candidates. To develop such a model, we focused on the C3HeB/FeJ Kramnik's mouse forming hypoxic, encapsulated granulomas with a caseous necrotic center following Mycobacterium tuberculosis infection.

IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response.

During chronic infection with Mycobacterium tuberculosis (Mtb), bacilli multiplication is constrained within lung granulomas until excessive inflammation destroys the lung. Neutrophils are recruited early and participate in granuloma formation, but excessive neutrophilia exacerbates the tuberculosis disease. Neutrophils thus appear as potential targets for therapeutic interventions, especially in patients for whom no antibiotic treatment is possible.

An in vitro model to assess the immunosuppressive effect of tick saliva on the mobilization of inflammatory monocyte-derived cells.

Tick-borne pathogens cause potent infections. These pathogens benefit from molecules contained in tick saliva that have evolved to modulate host innate and adaptive immune responses. This is called "saliva-activated transmission" and enables tick-borne pathogens to evade host immune responses.

Diminished metastasis in tetraspanin CD151-knockout mice.

Tetraspanin protein CD151 on tumor cells supports invasion and metastasis. In the present study, we show that host animal CD151 also plays a critical role. CD151-null mice showed markedly diminished experimental lung metastasis after injection of Lewis lung carcinoma or B16F10 melanoma cells.

Existence of CD8α-like dendritic cells with a conserved functional specialization and a common molecular signature in distant mammalian species.

The mouse lymphoid organ-resident CD8alpha(+) dendritic cell (DC) subset is specialized in Ag presentation to CD8(+) T cells. Recent evidence shows that mouse nonlymphoid tissue CD103(+) DCs and human blood DC Ag 3(+) DCs share similarities with CD8alpha(+) DCs. We address here whether the organization of DC subsets is conserved across mammals in terms of gene expression signatures, phenotypic characteristics, and functional specialization, independently of the tissue of origin.

Plasmacytoid dendritic cells migrate in afferent skin lymph.

Conventional dendritic cells enter lymph nodes by migrating from peripheral tissues via the lymphatic route, whereas plasmacytoid dendritic cells (pDC), also called IFN-producing cells (IPC), are described to gain nodes from blood via the high endothelial venules. We demonstrate here that IPC/pDC migrate in the afferent lymph of two large mammals. In sheep, injection of type A CpG oligodinucleotide (ODN) induced lymph cells to produce type I IFN.

Cervical duct cannulation in sheep for collection of afferent lymph dendritic cells from head tissues.

Pseudo-afferent cervical lymph-duct cannulation in a sheep model allows large amounts of lymph cells to be collected under physiological conditions, carrying immune signaling information from the head tissues, including oro-nasal mucosae. Importantly, large quantities of dendritic cells (DCs) of several subtypes are obtained (up to 8 million per overnight collection), as well as many other trafficking leukocytes. The technique includes three steps: removal of all head lymph nodes on one side (2 h), catheterization of cervical lymph ducts after 2 months (2-3 h) and collection/purification of lymph-cell subsets (4 h).

Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self.

The intestinal epithelium functions to absorb nutrients and to protect the organism against microbes. To prevent autoimmune attack on this vital tissue, T cell tolerance to intestinal self-antigens must be established. Central tolerance mechanisms involve medullary thymic epithelial cells (mTECs), which use endogenously expressed peripheral-tissue antigens (PTAs) to delete self-reactive thymocytes.

Migratory monocytes and granulocytes are major lymphatic carriers of Salmonella from tissue to draining lymph node.

Dendritic cells (DC) are recognized as sentinels, which capture antigens in tissue and migrate to the lymph node, where they initiate immune responses. However, when a vaccine strain of green fluorescent protein-expressing Salmonella abortusovis (SAO) was inoculated into sheep oral mucosa, it induced accumulation of myeloid non-DC in the subcapsular sinus and paracortex of the draining lymph node, and SAO was mainly found associated with these cells (granulocytes and macrophages) but rarely with DC. To analyze how bacteria reached lymph nodes, we used cervical pseudo-afferent lymph duct catheterization.

Probing leukocyte traffic in lymph from oro-nasal mucosae by cervical catheterization in a sheep model.

Lymph nodes are instructed via the lymph about ongoing events in tissues both during the steady state and under provoked inflammation. In order to probe for tissue-to-node transduction mechanisms, we have developed a novel in vivo technique of pseudo-afferent lymph collection from the oro-nasal mucosae which represent the main portals of entry of micro-organisms and efficient routes for vaccination. After lateral lymph node resection of the head, a network of lymph ducts was reconstructed as checked by lymphography.

Enrichment for a CD26hi SIRP- subset in lymph dendritic cells from the upper aero-digestive tract.

Dendritic cells (DC) have been reported to migrate in afferent lymph in the steady state. However, it is unknown whether DC traffic is modulated by the nature of the drained tissue. To analyze the influence of mucosal versus cutaneous microenvironments on the constitutive DC release, we exploited a novel technique of lymph cannulation in sheep, which allowed a comparison of afferent lymph DC migrating from the head mucosae [cervical DC (CerDC)] with DC migrating from skin [prescapular DC (PresDC)].