Pre-treatment of Nile tilapia (Oreochromis niloticus) with ozone nanobubbles improve efficacy of heat-killed Streptococcus agalactiae immersion vaccine

Nanobubble technology has shown appealing technical benefits and potential applications in aquaculture. We recently found that treatment with ozone nanobubbles (NB-O3) activated expression of several immune-related genes leading to effective response to subsequent exposure to fish pathogens. In this study, we investigated whether pre-treatment of Nile tilapia (Oreochromis niloticus) with NB-O3 can enhance specific immune responses and improve efficacy of immersion vaccination against Streptococcus agalactiae. Spleen and head kidney of fish in the vaccinated groups showed a substantial upregulation in expression levels of three immunoglobulin classes (IgM, IgD, and IgT) compared with the unvaccinated control groups. At day 21 post-immunization, the relative expression was greatest (approx. 3.2 to 4.1 folds). Both systemic and mucosal IgM antibodies were elicited in vaccinated groups. As the result, the cumulative survival rate of the vaccinated groups was found to be higher than that of the unvaccinated groups, with a relative percent survival (RPS) ranging from 52.9-70.5%. However, fish in the vaccinated groups that received pre-treatment with NB-O3, bacterial antigen uptakes, expression levels of IgM, IgD, and IgT, as well as the specific-IgM antibody levels and percent survival, were all slightly or significantly higher than that of the vaccinated group without pre-treatment with NB-O3. Taken together, our findings suggest that utilizing pre-treatment with NB-O3 may improve the immune response and efficacy of immersion vaccination in Nile tilapia.

T Cell Interactions in Mycobacterial Granulomas: Non-Specific T Cells Regulate Mycobacteria-Specific T Cells in Granulomatous Lesions

Infections with pathogenic mycobacteria are controlled by the formation of a unique structure known as a granuloma. The granuloma represents a host–pathogen interface where bacteria are killed and confined by the host response, but also where bacteria persist. Previous work has demonstrated that the T cell repertoire is heterogenous even at the single granuloma level. However, further work using pigeon cytochrome C (PCC) epitope-tagged BCG (PCC-BCG) and PCC-specific 5CC7 RAG−/− TCR transgenic (Tg) mice has demonstrated that a monoclonal T cell population is able to control infection. At the chronic stage of infection, granuloma-infiltrating T cells remain highly activated in wild-type mice, while T cells in the monoclonal T cell mice are anergic. We hypothesized that addition of an acutely activated non-specific T cell to the monoclonal T cell system could recapitulate the wild-type phenotype. Here we report that activated non-specific T cells have access to the granuloma and deliver a set of cytokines and chemokines to the lesions. Strikingly, non-specific T cells rescue BCG-specific T cells from anergy and enhance the function of BCG-specific T cells in the granuloma in the chronic phase of infection when bacterial antigen load is low. In addition, we find that these same non-specific T cells have an inhibitory effect on systemic BCG-specific T cells. Taken together, these data suggest that T cells non-specific for granuloma-inducing agents can alter the function of granuloma-specific T cells and have important roles in mycobacterial immunity and other granulomatous disorders.

ML218 HCl Is More Efficient Than Capsaicin in Inhibiting Bacterial Antigen-Induced Cal 27 Oral Cancer Cell Proliferation

The bacterial antigen, lipopolysaccharide (LPS) and disruptions in calcium channels are independently known to influence oral cancer progression. Previously, we found that bacterial antigens, LPS and lipoteichoic acid (LTA) act as confounders during the action of capsaicin on Cal 27 oral cancer proliferation. As calcium channel drugs may affect oral cancer cell proliferation, we investigated the effect of ML218 HCl, a T-type voltage-gated calcium channel blocker, on the proliferation of Cal 27 oral cancer cells. We hypothesized that ML218 HCl could effectively reduce LPS-induced oral cancer cell proliferation. LPS and LTA antigens were added to Cal 27 oral cancer cells either prior to and/or concurrently with ML218 HCl treatment, and the efficacy of the treatment was evaluated by measuring Cal 27 proliferation, cell death and apoptosis. ML218 HCl inhibited oral cancer cell proliferation, increased apoptosis and cell death, but their efficacy was significantly reduced in the presence of bacterial antigens. ML218 HCl proved more effective than capsaicin in reducing bacterial antigen-induced Cal 27 oral cancer cell proliferation. Our results also suggest an interplay of proliferation factors during the bacterial antigens and calcium channel drug interaction in Cal 27. Bacterial antigen reduction of drug efficacy should be considered for developing newer pharmacological agents or testing the efficacy of the existing oral cancer chemotherapeutic agents. Finally, voltage gated calcium channel drugs should be considered for future oral cancer research.

Bacterial Translocation as Inflammatory Driver in Crohn’s Disease

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract responsible for intestinal lesions. The multifactorial etiology attributed to CD includes a combination of environmental and host susceptibility factors, which result in an impaired host–microbe gut interaction. Bacterial overgrowth and dysbiosis, increased intestinal barrier permeability, and altered inflammatory responses in patients with CD have been described in the past. Those events explain the pathogenesis of luminal translocation of bacteria or its products into the blood, a frequent event in CD, which, in turn, favors a sustained inflammatory response in these patients. In this review, we navigate through the interaction between bacterial antigen translocation, permeability of the intestinal barrier, immunologic response of the host, and genetic predisposition as a combined effect on the inflammatory response observed in CD. Several lines of evidence support that translocation of bacterial products leads to uncontrolled inflammation in CD patients, and as a matter of fact, the presence of gut bacterial genomic fragments at a systemic level constitutes a marker for increased risk of relapse among CD patients. Also, the significant percentage of CD patients who lose response to biologic therapies may be influenced by the translocation of bacterial products, which are well-known drivers of proinflammatory cytokine production by host immune cells. Further mechanistic studies evaluating cellular and humoral immune responses, gut microbiota alterations, and genetic predisposition will help clinicians to better control and personalize the management of CD patients in the future.

Biomimetic nanomedicine-triggered in situ vaccination for innate and adaptive immunity activations for bacterial osteomyelitis treatment

The development of bacterial vaccines for inducing immunoresponse against infectious diseases such as osteomyelitis is of great significance and importance. However, the responsiveness of bacterial immunotherapy remains far from being satisfactory largely due to the erratic antigen epitopes of bacteria. Herein, we report an in situ vaccination strategy for the immunotherapy of bacterial infection based on an osteomyelitis model using a biomimetic nanomedicine named as HMMP, which was constructed by engineering PpIX-encapsulated hollow MnOx with a hybrid membrane exfoliated from both macrophage and tumor cell lines. The as-established HMMP features a burst bacterial antigen release as the in situ vaccine by the augmented sonodynamic treatment, and the resultant priming of antigen presenting cells for the following activations of both cellular and humoral adaptive immunities against bacterial infections. This treatment regimen not only triggers initial bacterial regression in established osteomyelitis model, also simultaneously generate robust systemic antibacterial immunity against poorly immunogenic secondary osteomyelitis in the contralateral knee as well, and additionally, confers long-lasting bacteria-specific immune memory responses to prevent infection relapse. Thus, our study provides a proof of concept of in situ vaccination for the activation of both innate and adaptive antibacterial immune responses, providing an individual-independent bacterial immunotherapy.

Production of Antibodies in Egg Whites of Chickens

Background: IgM, which participates in the primary immune response, is the primary antibody in egg whites. There is scant information about the production of antibodies in egg whites. This study describes the preparation of antibodies against a bacterial antigen, staphylococcal protein-A. Methods: The detection of antibodies against staphylococcal protein-A in egg white was performed by ELISA, and the antibodies were purified by protein-A affinity chromatography. Agglutination inhibition of Staphylococcus aureus Cowan I strains by purified antibodies against protein-A in vitro was investigated. Results: ELISA showed the production of antibodies against staphylococcal protein-A in the egg whites of layer hens. The antibodies were separated using affinity chromatography. The agglutination of Staphylococcus aureus Cowan I strains occurred when the purified antibodies were incubated with S. aureus. Conclusion: The results showed that it is possible to produce antibodies against bacterial antigens in egg whites, which can have industrial applications in the preparation of antibodies for immunotherapy of infectious diseases.

VACCINE DEVELOPMENT- A COMPLEX SCIENCE

Several human vaccinations were created at the end of the nineteenth century, Smallpox, rabies, plague, cholera, and typhoid vaccinations are among them. Major things to acknowledge before vaccine preparation is that we have to isolate the antibody firstly which our body has produced against the pathogen and what is the composition of that antibody and also the structure of an antibody. A vaccine is administered to induce immunity in an individual’s body. Typically, the manufacture of vaccine uses viral or bacterial antigen in it. It may be killed or attenuated vaccine (live but less virulent). The foremost step to produce a vaccine is to select the strains for the vaccine and to culture the strain or microorganism. These two steps are collectively known as the upstream process. This is further followed by isolation and purification of the microorganism and then after the inactivation of the organism which is used for vaccine preparation formulation of vaccine begins. The last step is to check quality control and then further lot release; all of these steps are included in downstream processing. Mostly used vaccines lack efficiency, potency and safety. To take the vaccine preparation to next level, the introduction of monoclonal antibodies, recombinant DNA, and protein engineering have been accelerated knowledge of pathogenic mechanisms. This review provides a new approach to the development of the succeeding generation of vaccines.

Molecular biology of Hodgkin lymphoma

Classical Hodgkin lymphoma (cHL) is unique among lymphoid malignancies in several key biological features. (i) The Hodgkin and Reed-Sternberg (HRS) tumor cells are rare among an extensive and complex microenvironment. (ii) They derive from B cells, but have largely lost the B-cell typical gene expression program. (iii) Their specific origin appears to be pre-apoptotic germinal center (GC) B cells. (iv) They consistently develop bi- or multinucleated Reed-Sternberg cells from mononuclear Hodgkin cells. (v) They show constitutive activation of numerous signaling pathways. Recent studies have begun to uncover the basis of these specific features of cHL: HRS cells actively orchestrate their complex microenvironment and attract many distinct subsets of immune cells into the affected tissues, to support their survival and proliferation, and to create an immunosuppressive environment. Reed-Sternberg cells are generated by incomplete cytokinesis and refusion of Hodgkin cells. Epstein-Barr virus (EBV) plays a major role in the rescue of crippled GC B cells from apoptosis and hence is a main player in early steps of lymphomagenesis of EBV+ cHL cases. The analysis of the landscape of genetic lesions in HRS cells so far did not reveal any highly recurrent HRS cell-specific lesions, but major roles of genetic lesions in members of the NF-κB and JAK/STAT pathways and of factors of immune evasion. It is perhaps the combination of the genetic lesions and the peculiar cellular origin of HRS cells that are disease defining. A combination of such genetic lesions and multiple cellular interactions with cells in the microenvironment causes the constitutive activation of many signaling pathways, often interacting in complex fashions. In nodular lymphocyte predominant Hodgkin lymphoma, the GC B cell-derived tumor cells have largely retained their typical GC B-cell expression program and follicular microenvironment. For IgD-positive cases, bacterial antigen triggering has recently been implicated in early stages of its pathogenesis.

Anatomopathological and immunohistochemical findings of natural Brucella abortus infection in buffalo uterin and peri-vaginal lymph nodes

The present work aimed to evaluate the macro and microscopic lesions and the distribution of Brucella sp. in the reproductive tract of seropositive female buffaloes to brucellosis. Nineteen genital tracts and eighteen peri-vaginal lymph nodes from previous serum reagent animals to brucella were collected from slaughterhouse, processed and submitted to Fisher's exact test (5%). It was not observed uterine macroscopic lesions from non-pregnant and pregnant until the four month, as well as are infrequent in the peri-vaginal lymph nodes. Microscopical lesions were found as lymphocyte clustering in caruncle in the placentome, necrosis and desquamation of chorionic cells, and in the peri-vaginal lymph nodes may occur oedema, increased neutrophil frequency, lymphocyte depletion, lymphoid hyperplasia, congestion, haemorrhage, and vasculitis. Thus, the IHC displayed great sensitivity to identify the presence of the bacterial antigen in tissues of seropositive animals of this species.