Cross-Reactive Effects of Vaccines: Heterologous Immunity between Tetanus and Chlamydia

Vaccines can have heterologous effects on the immune system, i.e., effects other than triggering an immune response against the disease targeted by the vaccine. We investigated whether monoclonal antibodies (mAbs) specific for tetanus could cross-react with Chlamydia and confer heterologous protection against chlamydial infection. The capability of two tetanus-specific mAbs, namely mAb26 and mAb51, to prevent chlamydial infection has been assessed: (i) in vitro, by performing a neutralization assay using human conjunctival epithelial (HCjE) cells infected with Chlamydia trachomatis serovar B, and (ii) in vivo, by using a guinea pig model of Chlamydia caviae-induced inclusion conjunctivitis. The mAb26 has been superior in comparison with mAb51 in the prevention of chlamydial infection in HCjE cells. The mAb26 has conferred approximate to 40% inhibition of the infection, compared to less than 5% inhibition in the presence of the mAb51. In vivo, mAb26 significantly diminished ocular pathology intensity in guinea pigs infected with C. caviae compared to either the mAb51-treated or sham-treated guinea pigs. Our data provide insights that tetanus immunization generates antibodies which induce heterologous chlamydial immunity and promote protection beyond the intended target pathogen

BRAF V600E MUTATIONS IN METASTATIC MELANOMA - CASE REPORT

The treatment of metastatic melanoma represents a challenge. Vemurafenib, a selective BRAF kinase inhibitor, is a new medicine against carcinoma. Recently, it has been shown that it raises the survival rate among patients with metastatic melanoma who have BRAFV600mutation. This work will discuss new approaches to the treatment of patients with metastatic melanoma, who have been proved to have BRAF V600 mutation and we will present the case of a female patient with whom the clinical study with Vemurafenib has been started

Cooperative binding of anti-tetanus toxin monoclonal antibodies: Implications for designing an efficient biclonal preparation to prevent tetanus toxin intoxication

Oligoclonal combinations of several monoclonal antibodies (MAbs) are being considered for the treatment of various infectious pathologies. These combinations are less sensitive to antigen structural changes than individual MAbs; at the same time, their characteristics can be more efficiently controlled than those of polyclonal antibodies. The main goal of this study was to evaluate the binding characteristics of six biclonal equimolar preparations (BEP) of tetanus toxin (TeNT)-specific MAbs and to investigate how the MAb combination influences the BEPs' protective capacity. We show that a combination of TeNT-specific MAbs, which not only bind TeNT but also exert positive cooperative effects, results in a BEP with superior binding characteristics and protective capacity, when compared with the individual component MAbs. Furthermore, we show that a MAb with only partial protective capacity but positive effects on the binding of the other BEP component can be used as a valuable constituent of the BEP. (C) 2018 Elsevier Ltd. All rights reserved

The Effect of Ultrasonic Treatment on the Binding of the Inclusion Complex β-Cyclodextrin-peppermint Oil with Cellulose Material

The purpose of the research was to measure the increase in the binding of inclusion complexes β-cyclodextrin-peppermint oil (β-CD_PM) to cellulose in cotton and cotton/polyester material with BTCA as the crosslinking agent by applying an ultrasonic bath at room temperature and a frequency of 80 kHz for 10 min. After sonication, the samples were left in a bath for 24 h after which they were dried, thermocondensed and subjected to a number of wash cycles. The treated samples were analysed with Attenuated total reflection (ATR) units heated up to 300 °C (Golden Gate (FTIR-ATR)) to monitor chemical changes indicative of crosslinking, while physico-chemical changes in the samples were monitored by using Fourier transform infrared spectroscopy (FTIR-ATR). Mechanical properties were measured according to EN ISO 13934-1:1999, and coloristic changes were evaluated by the whiteness degree according to CIE (WCIE) and the yellowing index (YI), while antimicrobial activity was determined according to AATCC TM 147-2016. The results show a physico-chemical modification of the UZV-treated cellulosic material. Moreover, partial antimicrobial efficacy on Gram-negative bacteria was confirmed for treated fabrics

Induction of decreased fecundity by tetanus toxoid hyper-immunization in C57BL/6 mice depends on the applied adjuvant

It has already been shown that tetanus toxoid (TTd) hyper-immunization is a suitable experimental method for creating the animal model of antiphospholipid syndrome (APS) in BALB/c mice. The severity of APS pathology in BALB/c mice mainly correlates to the affinity of anti-beta(2) glycoprotein I (beta(2)GPI) antibodies. In this study we have investigated reproductive pathology induced in C57BL/6 mice by TTd hyper-immunization using a combination of different pretreatments (complete Freund's adjuvant or glycerol) and adjuvants (alhydrogel or glycerol). A decrease in fecundity was recorded in only C57BL/6 mice immunized with alhydrogel adjuvant, irrespective of the kind of applied pretreatment; it was associated with an increase in abundance of low affinity anti-beta(2)GPI IgG antibodies and Th1 prevalence

Phenotypic and functional characteristics of splenocytes in tetanus toxoid-hyperimmunized Balb/c mice is influenced by the context of tetanus toxoid application

Purpose/Objective: The hyperimmunization with tetanus toxoid (TTd) induces protective TTd-specific as well as autoreactive b2-glycoprotein I (b2GPI)-specific immune responses in BALB/c mice. The overall immune response characteristics, especially its pathogenic potential, depended on adjuvants applied prior and in combination with TTd. Beside structural homology between TTd and b2GPI, tolerance toward b2GPI could be impaired by adjuvants acting as polyclonal stimulators. In order to clarify the impact of adjuvants, phenotypic and functional analyses of immune system cells within spleen were done upon immunization completion. Materials and methods: Non- or CFA-pretreated BALB/c mice were immunized with TTd (3 · 100 lg/dose; 2-week intervals) mixed with alum or 2.5M glycerol. Ex vivo analyses of CD3, CD4, CD8, CD19, CD 25, CD27 and mIgM expression on age-matched control and immunized mice’s splenocytes were done by flow cytometry. Changes in TLR2, TLR4 and TLR9 expression were assessed indirectly, by measuring cytokine production, following in vitro stimulation of splenocytes with appropriate agonist. Results: TTd-immunization diminished CD27 expression on T cells implying on their differentiation into potent effector cells. T cell activation (increase in CD25 expression and the raise of percentage of CD4+ CD8+ CD3+ ) and B cell activation (rise in percentage of CD19+ CD25+ cells and the increase of mIgM density) occurred in all immunized mice, being more intensive in CFA-pretreated groups. Irrespective to the applied immunization protocol, statistically significant rise in abundance of CD4- CD8- cells (often cited as cells having suppressive potential) within T cell pool was registered too. Differences in cytokines production (IL4, IL10, IFNc) registered upon in vitro stimulation with peptidoglycan, LPS and CpG ODN implied on context-dependant modulation of TLR2, TLR4 and TLR9 expression on splenocytes. Conclusions: TTd-hyperimmunization promoted concomitant rise in abundance of activated cells and the cells that have suppressive potential. This could be regarded as an attempt of the system to retain control. Imbalance in percentages and activities between activated cells and those having suppressive potential, highly influenced by the context of TTd application, is most likely the cause for the observed pathology appearance after TTd hyperimmunization

Role of molecular mimicry and polyclonal cell activation in the induction of pathogenic beta 2-glycoprotein I-directed immune response in Balb/c mice upon hyperimmunization with tetanus toxoid

It is known that tetanus toxoid (TTd)-hyperimmunization induces increased titer of sera beta 2-glycoprotein I (beta 2GPI)-specific antibodies (Abs) in Balb/c mice. The concentrations of such induced anti-beta 2GPI Abs as well as their pathogenic potential are strongly influenced by the context of TTd application. beta 2GPI-specific immune response is established as a part of TTd-specific immune response by molecular mimicry mechanism due to structural homology between TTd and beta 2GPI. This finding is supported by the following facts: (1) cross-reactive Abs that recognize both TTd and beta 2GPI epitopes are present in Balb/c mice sera; (2) anti-TTd Abs secretion in splenic cultures is induced after beta 2GPI stimulation and vice versa. However, analyses of (1) IL-10 production following in vitro stimulation of immunized Balb/c mice splenocytes by TTd, beta 2GPI or glutaraldehyde-treated beta 2GPI and (2) specific impact of ConA and agonists of TLR2, TLR4, and TLR9 on anti-TTd and autoreactive Abs secretion strongly imply that these two branches of the TTd-induced immune response do not use identical cell populations and are regulated in a different way. Results presented in this paper describe that structural homology between foreign and self-antigens could focus mounted autoreactive immune response toward specific self-structure, but the context of antigen application, including a history of previous immune stimulations and adjuvants applied together with the antigen, are the main factors which determine the outcome of the induced immune response

The role of radiotherapy in combined treatment for locally advanced breast cancer with ipsilateral supraclavicular metastases

Background: Locally advanced breast cancer (LABC) includes a heterogeneous group of breast neoplasms classified from stage IIB, IIIA to IIIB. LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease is included in the stage IV (but regional stage IV). Purpose of this study was to assess the role of radiotherapy (RT) in combined treatment with systemic therapy (chemotherapy and hormonotherapy) in LABC with ipsilateral supraclavicular adenopathy. Methods: In 5-year period 45 patients with LABC and ipsilateral supraclavicular metastases were treated with radiotherapy and chemo- or hormonotherapy depending on the physical condition, age and steroid receptors (ER, PGR) content. Twenty patients received TD 30 Gy in 10 fractions on breast and regional lymph nodes and 25 patients received TD 51 Gy in 15 fractions on the breast and TD 45 Gy in 15 fractions on regional lymph nodes. Twenty-three patients received chemotherapy (CMF or FAC), 10 received hormonotherapy, and 12 received both chemo- and hormonotherapy. Results: After finishing complete treatment the overall response rate was 93.3%. Complete response was 20% and partial response was 73.3%. Locoregional relapse occurred in 5 patients and distant metastases occurred in 10 patients. Conclusion: Treatment of LABC with ipsilateral supraclavicular lymph node involvement should be aggressive, what means combined radiotherapy and systemic chemo-hormonotherapy. Such treatment provides for these patients maximum chance of long-term disease - free and overall survival

Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers

Natural antibodies (NAbs) are present in circulation even before the exposure to antigen and they exert various biological functions. They are polyreactive and mainly represented by immunoglobulin M (IgM), which is the first antibody produced in an ongoing immune response to infection and/or immunization. IgM is always secreted as a polymer with predominant pentameric structure, although other polymeric forms such as hexamer can be also formed. The biological functions of hexameric IgM are still not known and it is proposed that its existence as a NAb could be deleterious. However, the nature of IgM hexamers has not been investigated yet. In this paper, we have tested the expression of natural idiotope and antigenic specificities of pentameric and hexameric IgM polymers originating from sera of patients with Waldenstrom's macroglobulinemia, as well as patients suffering from recurrent urinary bacterial infections. We demonstrate that although pentameric IgM polymers can exist as natural and immune antibodies, IgM hexamers are exclusively immune and do not exist as NAbs