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Our understanding of immunity to filarial infection is enigmatic and continues to be passionately debated. The mechanisms whereby filarial nematodes are killed in vivo and how these parasites avoid these mechanisms are poorly understood. Although vaccination studies in permissive animals took off seven decades ago, the exact mechanisms driving protective immunity are extensively being investigated. Currently, little is known regarding the collective functions or counter-regulatory mechanisms of the antibody isotypes in filarial infection with respect to protective immunity. Establishing the functional role of antibody isotypes and cytokines in the various infection phenotypes can contribute immensely to current knowledge in filarial immunology. This paper reviews insight into protective immunity in filarial infection with focus on humoral and cellular responses from animal models and human studies. [ABSTRACT FROM AUTHOR]

Invertebrate immune priming, and other forms of innate immune memory in bacteria, plants, and mammals, modulate the post-infection resistance, tolerance, and survival phenotypes of individuals previously exposed to microbes. By influencing the probability of both transmission and disease-induced mortality, priming is likely to have a significant impact on disease dynamics. Two alternative models have been proposed as frameworks for the role of priming in infected populations, but the differences in their underlying key assumptions yield very different predictions for the effect of priming on disease dynamics. By examining these assumptions from the lens of within-host dynamics, the model presented in this paper demonstrates that priming systems can be characterized along a continuous dose-response gradient that unites these disparate frameworks. Moreover, it facilitates the incorporation of different kinds of immunological plasticity mechanisms, as well as the exposure probability and transmission characteristics of parasites. Simulating the interaction of these thresholds with the diversity of parasite life history strategies and distributions predicts that priming may actually inflate disease prevalence under certain conditions. Thus, priming of innate immune systems may act analogously to leaky vaccines and drive parasite virulence evolution. The results underscore the need for experimental studies that determine dose response curves for the both the probability of becoming primed following primary parasite exposure and shifts in resistance and tolerance in infected primed hosts. This framework is applicable to a variety of systems that show immunological memory. [ABSTRACT FROM AUTHOR]

B cells have an important pathogenic role in the development of type 1 diabetes in the non-obese diabetic ( NOD) mouse. We have previously reported that NOD mice display an increased percentage of TACIhigh-expressing B cells compared with C57 BL/6 mice and this trait is linked to chromosomes 1 and 8. In this paper the genetic association of the transmembrane activator, calcium modulator and cyclophilin ligand interactor ( TACI) trait was confirmed using double congenic NOD. B6C1/Idd22 mice. TACI ligation by a proliferation-inducing ligand ( APRIL) has been shown to influence plasma cell differentiation, immunoglobulin production and isotype switch. Hence, the functional consequence of the up-regulation of TACI on NOD B cells was analysed both in vitro and in vivo. NOD B cells stimulated with APRIL showed an enhanced plasma cell differentiation and class switch to IgG and IgA compared with B cells from C57 BL/6 mice. Moreover, flow cytometry analyses revealed that germinal centre B cells in NOD failed to down-regulate TACI. Availability of the TACI ligand B-cell activating factor ( BAFF) has been shown to be a limiting factor in the germinal centre reaction. In line with this, upon immunization with 4-hydroxy-3-nitrophenylacetyl hapten-conjugated hen egg lysozyme, NOD mice produced higher titres of low-affinity antibodies compared with C57 BL/6 mice. This observation was supported by the detection of increased levels of BAFF in NOD germinal centres after immunization compared with C57 BL/6 by immunofluorescence. Our results support the hypothesis that increased TACI expression on NOD B cells contributes to the pathogenesis of type 1 diabetes in the NOD mouse. [ABSTRACT FROM AUTHOR]

Antibody labeling has been conducted extensively for structure determination using both X‐ray crystallography and electron microscopy (EM). However, establishing target‐specific antibodies is a prerequisite for applying antibody‐assisted structural analysis. To expand the applicability of this strategy, an alternative method has been developed to prepare an antibody complex by inserting an exogenous epitope into the target. It has already been demonstrated that the Fab of the NZ‐1 monoclonal antibody can form a stable complex with a target containing a PA12 tag as an inserted epitope. Nevertheless, it was also found that complex formation through the inserted PA12 tag inevitably caused structural changes around the insertion site on the target. Here, an attempt was made to improve the tag‐insertion method, and it was consequently discovered that an alternate tag (PA14) could replace various loops on the target without inducing large structural changes. Crystallographic analysis demonstrated that the inserted PA14 tag adopts a loop‐like conformation with closed ends in the antigen‐binding pocket of the NZ‐1 Fab. Due to proximity of the termini in the bound conformation, the more optimal PA14 tag had only a minor impact on the target structure. In fact, the PA14 tag could also be inserted into a sterically hindered loop for labeling. Molecular‐dynamics simulations also showed a rigid structure for the target regardless of PA14 insertion and complex formation with the NZ‐1 Fab. Using this improved labeling technique, negative‐stain EM was performed on a bacterial site‐2 protease, which enabled an approximation of the domain arrangement based on the docking mode of the NZ‐1 Fab. [ABSTRACT FROM AUTHOR]

The article focuses on the Dr. Heinz Karger Prize given by Dr. Heinz Karger Memorial Foundation which invites the submission of papers on the subjects "Antibodies With Intrinsic Biological Activity," and "Intestinal Absorption of Peptides." Manuscripts shall not exceed 20 typewritten pages, including illustrations, tables and bibliography. The winning paper will be published in English in one of the Karger journals. The Council of the Foundation will judge the papers and confer the prize.

The amount and distribution of proteins of the light-harvesting complex associated with photosystem II (PS II) were investigated using immunogold labelling of chloroplasts of wheat (Triticum aestivum L. cv. Walde). The seedlings were grown in weak red light (16 mW m-2) after imbibition of grains with SAN-9789 (Norflurazon, 0.028 to 28 mg l-1). Chloroplasts of these plants exhibited thylakoids with different degrees of stacking. Thylakoids of untreated plants grown in a greenhouse had most gold particles per unit membrane length in both appressed and non-appressed regions compared to red light grown plants. The ratios of labelling between appressed and non-appressed membranes were fairly constant in red light- and greenhouse-grown plants. The labelling densities were 2.5-3 times higher in the appressed thylakoids compared to the non-appressed thylakoids. However, at a SAN concentration of 2.8 mg l-1 there was a sharp decrease in thylakoid appressions and in labelling density of both appressed and non-appressed membranes. The total amount of particles per chloroplast was also much lower as compared to that at lower SAN concentrations. Plants treated with the highest concentration of SAN (28 mg l-1) contained chloroplasts devoid of normal grana structures. In these plastids, the thylakoids were elongated and single. The labelling density in these membranes was ca 50% of that observed at 2.8 mg l-1. This paper thus supports earlier observations that proteins of the light-harvesting complex of PS II (LHC II) are mainly localized in the appressed regions of the grana membranes, and may be involved in the formation of grana. [ABSTRACT FROM AUTHOR]

Cystatins are physiological inhibitors of cysteine proteinases which are widely distributed in human tissues and fluids. In the present study we analysed both the cystatin activity and the different cystatin isoforms in gingival crevicular fluid and saliva samples of nine periodontitis patients. All crevicular fluid samples, which were collected with filter paper points, showed cystatin activity ranging from 7-67 units/mg protein. The mean cystatin activity (24 units/mg protein) was significantly lower (p < 0.05) than that of the saliva samples (mean 93 units/mg protein). The cystatin isoforms in the crevicular fluid were further characterized by immunoblotting with specific antibodies against cystatin C, S, SN and A. While they were clearly present in saliva, cystatin C, cystatin S and cystatin SN could not be detected in any of the crevicular fluid samples. Remarkably, cystatin A was found in all the crevicular fluids as well as in the saliva samples. It is concluded that the cystatin activity found in crevicular fluid is caused, at least partially, by cystatin A. Furthermore, the gingival crevicular fluid is not a major contributor of cystatin C, S and SN activity in saliva. [ABSTRACT FROM AUTHOR]

The structure of the proteomannans from the cell-wall mutant Candida sp. and its parent strain was further studied by immunochemical methods. Alkaline titration showed that the phosphate is present in the form of diester and mild acid treatment released mannose from both of the mannans. In the wild-type mannan, the phosphorylated side-chain oligosaccharides gave 85 % inhibition and a mannopentaose side chain having α1 -3 linkage in the nonreducing terminal also gave 40 % inhibition in the homologous precipitin reaction. This indicates that the immunodominant side chain of the Candida sp. wild type mannan is the phosphorylated mannopentaose which has an (α1- 3)-Linked nonreducing terminal. In the mutant system, a significant reactivity in the cross reaction between the mutant antiserum and Kloeckera brevis mannan indicates that the immunodeterminant of the mutant mannan may be a structural analogue of the side-chain oligosaccharide from K. brevis, which has phosphorylated (α1-2)-linked mannotriose. However, no definite results were obtained in the inhibition studies. On the basis of the results from chemical, enzymatical and immunological experiments, the side-chain structure and macromolecular models of Candida sp. wild-type and mutant mannans are proposed. [ABSTRACT FROM AUTHOR]

This paper describes a procedure for analysing multiple antibody reactivities that explores a commercially available immunoblot system, and is based on a double staining of nitrocellulose membranes, revealing both antibody reactivities and the migration position of the blotted proteins in the membrane. Quantification of both stainings by densitometry allowed the accurate superposition of the immunoreactivity and total protein profiles of each lane. Moreover, the protein stainings of the different lanes could be adjusted with a simple-scale transformation algorithm, correcting for possible distortions during electrophoretic migration, and allowing for the precise comparison of the immunoreactivity profiles in different lanes. The procedure is discriminatory enough to identify unique reactivity patterns in random pools of 104 activated B cells, and to define strain-specific natural antibody repertoires. The utility of this immunoblot method as an assay for simultaneously scoring multiple reactivities to hundreds of antigens in complex mixtures of antibodies, and thus defining antibody repertoires in a global manner, is discussed. [ABSTRACT FROM AUTHOR]

X-irradiated (250 rad), cyclophosphamide-treated or Atx A mice injected with syngeneic trinitrophenylated spleen cells (TNP-SC) and footpad challenged with syngeneic lymphoblasts generated delayed-type hypersensitivity (DTH) responses 24, 48 and 72 h after challenge. The syngeneic-DTH (syn-DTH) response was mediated by Lyt-1+ cells and suppressed with Lyt-1+2+3+, I-Jk+ cells. The suppressor cells were obtained from spleens or thymuses of normal syngeneic mice. Suppressor factor (SF) was extracted or released from Lyt-1+2+3+, I-Jk+ cells obtained from normal A mice (but not from X-irradiated A mice). The factor blocked the DTH responses of X-irradiated mice injected with syngeneic TNP-SC and challenged with syngeneic lymphoblasts when injected into the mice both at the induction phase and the elicitation phase of the DTH. The factor failed to abrogate allogeneic and xenogeneic DTH. However, allogeneic factor (derived from C57BL/6 mice) abolished the syn-DTH response of mice injected with syngeneic TNP-SC and challenged with syngeneic lymphoblasts. The SF was produced by Lyt-1+2+3+, I-Jk+ T cells or by thymocytes. The combined extracted product of Lyt-1+ and Lyt-2+ cells did not abrogate the syn-DTH response. Normal spleen cells depleted of phagocytes by a magnetic procedure also produced the SF. These findings indicate, therefore, that suppressive factor (or factors; see Discussion of the accompanying paper, Ref.17) controls the immunological autoreactivity against syngeneic TNP-SC. [ABSTRACT FROM AUTHOR]

As described in an accompanying paper, trinitrophenyl (TNP) modification of pork insulin (PI) at the A1 glycine position allows this molecule to stimulate a proliferative response in H-2b (B10) mice. We now show that this antigen stimulates low IgG responses in the same strain of mice. Our results show that T-cell help and proliferation may therefore be regulated independently. [ABSTRACT FROM AUTHOR]

MRL-lpr mice and their congenic counterparts MRL- + spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL- + and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL- + mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CRA PEC. The defect could not be explained by a failure of M RL- + or M RL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: (i) the failure of antigen-presenting cells in MRL- + and MRL-lpr to provide the necessary signals to immunocompetent T cells, this defect not being associated with the lpr gene, and (ii) the lpr gene controlled outgrowth of a unique T-cell population that cannot respond in our assay system. [ABSTRACT FROM AUTHOR]

T-colony formation can be induced in PHA-stimulated peripheral blood mononuclear cells (PBM) from man, but not in PHA-stimulated purified T cells, the latter requiring the presence of factors produced by PHA-stimulated PBM and termed T-colony promoting activity (TCPA). In this paper, we demonstrate that interleukin-2 (IL-2), the growth hormone of T lymphocytes, controls T-colony formation. We show that: (i) IL-2 activity and TCPA produced by PHA-activated PBM are co-purified by gel filtration and chromatography on blue agarose, a procedure which yields a 850-fold IL-2 purification; (ii) recombinant IL-2, produced by genetically manipulated Eseherichia coli, can induce T-colony formation in PHA-stimulated purified T cells; (iii) Monoclonal antibody against the IL-2 receptor (anti-Tac antibody) completely inhibits the T-colony formation in PHA-stimulated PBM when directly added to the culture system. [ABSTRACT FROM AUTHOR]

Several hybridoma cell lines secreting NP-specific, murine IgE antibodies were generated by fusion of P3-X20 (γ,κ) tumour cells with spleen cells from (BALB/c x C57Bl/6)F1 (CB6F1) mice previously immunized with NP-ovalbumin. Four subclones (designated NP-ε-3.57, NP-ε-15,88, NP-ε-91,58 and NP-ε-95,31) were propagated in vivo and milligram quantities of the corresponding IgE antibodies were purified from ascitic fluid by gel filtration, ion exchange chromatography and affinity chromatography. Immunological analyses and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDSPAGE) indicated that NP-ε-15,88, NP-ε-91,58 and NP-ε-95.31 all possessed λ1 (or possibly λ3) light chains; and that NP-ε-3,57 possessed λ2 light chains; NP-&elipson;-95,31 also expressed the P3-X20 derived, MOPC-21 κ light chain. Radioallergosorbent test (RAST) titration curves, generated from the interaction of the four monoclonal IgE antibodies with NP-BSA attached to paper discs (NP-BSA-P) were found to be non-overlapping. Measurements of the relative amounts of NP-ε-aminocaproic acid (NP-CAP) and 4-hydro-3-iodo-5-nitrophenylacetyl-ε- aminocaproic acid (NIP-CAP) that were required to inhibit by 50% the binding of the 4 IgE antibodies to NP-BSA-P indicated that these antibodies were all heteroclitic, since their affinity for NIP appeared to be higher than their affinity for NP. These results, in conjunction with other findings reported in the literature, suggested that the V regions of NP-specific IgE antibodies are similar to the V regions of NP-specific IgM and IgG antibodies, produced by the same mouse strains. Finally, in vitro histamine release measurements demonstrated that two of these monoclonal IgE antibodies could mediate antigen induced histamine release from passively sensitized rat peritoneal mast cells. [ABSTRACT FROM AUTHOR]

This paper describes the specificity of delayed-type hypersensitivity (DH) and antibody formation in the mouse to the tripeptide-enlarged hapten, 3-(p-azobenzenearsonate)-N-acetyl-L-tyrosylglycylglycine (A). Hapten A was coupled to phosphatidylethanolamine (PE) and incorporated into liposomal membranes (A PE-liposomes). DH was measured as footpad swelling and antibody formation by the enumeration of direct plaque-forming cells in the spleen. A-PE-liposomes mixed with the cationic, surface-active lipid, dimethyl dioctadecyl ammonium bromide (DDA) induce, on intracutaneous injection in mice, hapten-specific DH without a contribution by the carrier. With other haptenated liposomes it was not possible to induce DH to those haptens, including the closely related hapten 3-(p-azobenzenesulphonate)-N-acetyl-L-tyrosylglycylglycine (S). A-PE- and S-PE-liposomes evoke, after intravenous injection in mice, a humoral response. The antibody formation to A-PE-liposomes was thymus-independent. In this response a considerable cross reaction between haptens A and S was observed. [ABSTRACT FROM AUTHOR]

It has previously been shown that rats do not expel a primary infection of Nippostronglus brasiliensis during lactation. In the present paper, three aspects of the immune response of the lactating rat to the parasite were examined and compared with the response of non-lactating rats. Protective and reaginic antibodies were present in the circulation of rats first infected during lactation, in titres as high or higher than those in non-lactating controls. The intestinal mast cell response was similar both in timing and magnitude and lactating rats became susceptible to shock with the i.v. injection of antigen. Attention was drawn to the similarity between the response of the lactating rat and that of the neonate to this infection. [ABSTRACT FROM AUTHOR]

The article presents abstracts of various papers presented in the tenth meeting of the Scandinavian Society for Immunology. One of the papers presented is "HLA-DR matching and B-cell cross-match tests in cadaveric renal transplantation," by D. Albrechtcen, B.G. Solheim, N. Winter and E. Thorsby. Another paper "In vitro antibody synthesis in human cord blood lymphocyte cultures," by U. Andersson, A.G. Bird and S. Briuon analyzes the ability of human full-term cord blood lymphocytes to respond by antibody synthesis in vitro to various polyclonal B-lymphocyte activators.

The titer of anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) neutralizing antibodies (NAbs) in the human body is an essential reference for evaluating the acquired protective immunity and resistance to SARS‐CoV‐2 infection. In this study, a fluorescence‐quenching lateral flow immunoassay (FQ‐LFIA) is established for quantitative detection of anti‐SARS‐CoV‐2 NAbs in the sera of individuals who are vaccinated or infected within 10 min. The ultrabright aggregation‐induced emission properties encapsulated in nanoparticles, AIE490NP, are applied in the established FQ‐LFIA with gold nanoparticles to achieve a fluorescence "turn‐on" competitive immunoassay. Under optimized conditions, the FQ‐LFIA quantitatively detected 103 positive and 50 negative human serum samples with a limit of detection (LoD) of 1.29 IU mL−1. A strong correlation is present with the conventional pseudovirus‐based virus neutralization test (R2 = 0.9796, P < 0.0001). In contrast, the traditional LFIA with a "turn‐off" mode can only achieve a LoD of 11.06 IU mL−1. The FQ‐LFIA showed excellent sensitivity to anti‐SARS‐CoV‐2 NAbs. The intra‐ and inter‐assay precisions of the established method are below 15%. The established FQ‐LFIA has promising potential as a rapid and quantitative method for detecting anti‐SARS‐CoV‐2 NAbs. FQ‐LFIA can also be used to detect various biomarkers. [ABSTRACT FROM AUTHOR]

Hydrogels are prevailing drug delivery depots to improve antitumor efficacy and reduce systemic toxicity. However, the application of conventional free drug‐loaded hydrogel is hindered by poor drug penetration in solid tumors. Here, an injectable ferritin‐based nanocomposite hydrogel is constructed to facilitate tumor penetration and improve cancer chemoimmunotherapy. Specifically, doxorubicin‐loaded human ferritin (Dox@HFn) and oxidized dextran (Dex‐CHO) are used to construct the injectable hydrogel (Dox@HFn Gel) through the formation of pH‐sensitive Schiff‐base bonds. After peritumoral injection, the Dox@HFn Gel is retained locally for up to three weeks, and released intact Dox@HFn gradually, which can not only facilitate tumor penetration through active transcytosis but also induce immunogenic cell death (ICD) to tumor cells to generate an antitumor immune response. Combining with anti‐programmed death‐1 antibody (αPD‐1), Dox@HFn Gel induces remarkable regression of orthotopic 4T1 breast tumors, further elicits a strong systemic anti‐tumor immune response to effectively suppress tumor recurrence and lung metastasis of 4T1 tumors after surgical resection. Besides, the combination of Dox@HFn GelL with anti‐CD47 antibody (αCD47) inhibits postsurgical tumor recurrence of aggressive orthotopic glioblastoma tumor model and significantly extends mice survival. This work sheds light on the construction of local hydrogels to potentiate antitumor immune response for improved cancer therapy. [ABSTRACT FROM AUTHOR]

Background and Aim: Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy, characterized by the presence of some autoantibodies in the serum. This study aimed to evaluate the clinical significance of AMA‐M2, anti‐gp210 and anti‐sp100 antibody levels detected by multiplex bead‐based flow fluorescent immunoassay (MBFFI) in PBC. Methods: This study cohort included 238 PBC patients, 81 autoimmune hepatitis (AIH) patients, 62 systemic lupus erythematosus (SLE) patients, and 118 healthy controls. Serum AMA‐M2, anti‐gp210 and anti‐sp100 antibody were detected by MBFFI and immunoblotting assay (IBT). The relationship between three antibody levels and cirrhosis, liver function, cholestasis markers and therapeutic effect to ursodesoxycholic acid (UDCA) was evaluated in PBC. Results: MBFFI were presented good coincidence rate (87.39%–95.38%) with IBT. The level of AMA‐M2, anti‐gp210 and anti‐sp100 antibodies in PBC patients were higher than other disease group and healthy controls (p ＜.01). When compared with the healthy controls group, the AUC of AMA‐M2, anti‐gp210 and anti‐sp100 antibodies were 0.9245, 0.7619, and 0.6789, respectively. In addition, gp210 antibody levels have diagnostic value in patients with liver cirrhosis (AUC: 0.7567). We found that when combine detect these three antibodies, the sensitivity was higher than individually detection. High level of serum anti‐gp210 antibody could be related to worse liver function and more severe cholestasis in PBC patients. Moreover, serum antibody levels may decrease or remained flat in patients who responded well to UDCA. Conclusion: The detection of AMA‐M2, anti‐gp210 and anti‐sp100 antibody levels by MBFFI showed good performance in the diagnosis of PBC. Serum anti‐gp210 antibody level is related to cirrhosis, poor liver function and severe cholestasis in PBC. [ABSTRACT FROM AUTHOR]

Conditionally activated molecules, such as Probody therapeutics (PbTx), have recently been investigated to improve antitumoral response while reducing systemic toxicity. PbTx are engineered to be proteolytically activated by proteases that are preferentially active locally in the tumor microenvironment (TME). Here, we perform an exploratory study using our recently published quantitative systems pharmacology model, previously validated for other drugs, to evaluate the effectiveness and targeting specificity of an anti‐PD‐L1 PbTx compared to the non‐modified antibody. We have informed the model using the PbTx dynamics and pharmacokinetics published in the literature for anti‐PD‐L1 in patients with triple‐negative breast cancer (TNBC). Our results suggest masking of the antibody slightly decreases its efficacy, while increasing the localization of active therapeutic component in the TME. We also perform a parameter optimization for the PbTx design and drug dosing regimens to maximize the response rate. Although our results are specific to the case of TNBC, our findings are generalizable to any conditionally activated PbTx molecule in solid tumors and suggest that design of a highly effective and selective PbTx is feasible. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI), pembrolizumab and atezolizumab, were recently approved for treatment‐refractory triple‐negative breast cancer (TNBC), where those with Programmed death‐ligand 1 (PD‐L1) positive early‐stage disease had improved responses. ICIs are administered systemically in the clinic, however, reaching effective therapeutic dosing is challenging due to severe off‐tumor toxicities. As such, intratumoral (IT) injection is increasingly investigated as an alternative delivery approach. However, repeated administration, which sometimes is invasive, is required due to rapid drug clearance from the tumor caused by increased interstitial fluid pressure. To minimize off‐target drug biodistribution, we developed the nanofluidic drug‐eluting seed (NDES) platform for sustained intratumoral release of therapeutic via molecular diffusion. Here we compared drug biodistribution between the NDES, intraperitoneal (IP) and intratumoral (IT) injection using fluorescently labeled PD‐L1 monoclonal antibody (αPD‐L1). We used two syngeneic TNBC murine models, EMT6 and 4T1, that differ in PD‐L1 expression, immunogenicity, and transport phenotype. We investigated on‐target (tumor) and off‐target distribution using different treatment approaches. As radiotherapy is increasingly used in combination with immunotherapy, we sought to investigate its effect on αPD‐L1 tumor accumulation and systemic distribution. The NDES‐treated cohort displayed sustained levels of αPD‐L1 in the tumor over the study period of 14 days with significantly lower off‐target organ distribution, compared to the IP or IT injection. However, we observed differences in the biodistribution of αPD‐L1 across tumor models and with radiation pretreatment. Thus, we sought to extensively characterize the tumor properties via histological analysis, diffusion evaluation and nanoparticles contrast‐enhanced CT. Overall, we demonstrate that ICI delivery via NDES is an effective method for sustained on‐target tumor delivery across tumor models and combination treatments. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has caused a public health emergency in all sectors of society, including universities and other academic institutions in Cameroon. However, little is known concerning the real prevalence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections among student communities during the second wave of infection in Cameroon. This study aimed to estimate SARS‐CoV‐2 antibodies seroprevalence among participants in a university community in Cameroon. Methodology: A cross‐sectional study was conducted from March to April 2021 in 547 students aged ≥18 years during a mass diagnostic campaign at the School of Health Sciences of the Catholic University of Central Africa (ESS/UCAC). The anti‐SARS‐CoV‐2 antibody screening was done using the Panbio™ COVID‐19 IgG/IgM Rapid Diagnostic Test. Results: The overall seroprevalence of SARS‐CoV‐2 antibodies was 27%, of which 89.9% (n = 133) was IgG, 6.7% (n = 10) IgM and 3.4% (n = 5) IgG/IgM positive. The undergraduate students represented 79% (432/547) of the total population and were highly positive with anti‐SARS‐CoV‐2 antibodies 30% (130/432) as compared with postgraduate students 20% (23/115). The total antibody seropositivity was higher in males (34.4%) than females (24.9%). Several factors were associated with an increased risk of SARS‐CoV‐2 seroprevalence including the male gender (OR: 1.61 [95% confidence interval, CI 1.0–2.4]), specialization to medical laboratory (OR: 2.8 [95% CI 1.1–7.1]) and nursing sciences (OR: 2.6 [95% CI 1.1–6.2]). Conclusion: Our findings point to extensive and underreported circulation of SARS‐CoV‐2 in a university community during the second wave of infection in Cameroon, which likely resulted in artificially low case counts. [ABSTRACT FROM AUTHOR]

Heat and pH stability studies and experiments with organic solvents show that the A-antigens discussed in the preceding paper (Augustin, 1959c) are much more labile than the I-(‘inner ring’) antigens. Breakdown products and/or aggregates are produced which no longer precipitate with antisera to the original extracts, but act as inhibitors. Solutions of pollen allergens, on the other hand, are found to withstand even autoclaving for 15 min. at 20 atm. and vigorous boiling over the naked flame of a bunsen burner. None of the carbohydrates tested has a demonstrable effect on skin reactivity which is, however, destroyed by crystalline pepsin, crystalline trypsin, a crystalline mould protease and a tissue protease (a partially purified extract from rabbit spleen). It follows that the bulk of the allergens—if not all—are proteins. The relation of skin reactivity, immuno-electrophoretic patterns, carbohydrate and protein reactions to the selective destruction of the pollen antigens is investigated. Pollen components prove to have a somewhat wider range of electrophoretic mobilities than serum proteins and are probably as complicated a mixture. The most and least highly negatively charged components are without skin reactivity in allergic subjects. The skin reactive allergens appear to have the mobilities of α- and β-globulins. Not all the hay fever subjects react equally to all the components, and Cocksfoot and Timothy activity patterns vary in different subjects. [ABSTRACT FROM AUTHOR]

In this paper, the production of powder enriched in lactoferrin ( Lf) and immunoglobulin G ( IgG) from untreated feta cheese whey is studied. More specifically, the influence of transmembrane pressure (Δ p) and temperature on flux and separation ability during ultrafiltration combined with continuous diafiltration is investigated. Two different types of membranes were used, a spiral polyvinylidene fluoride ( PVDF) (molecular weight cut-off [ MWCO ∼ 75 kDa) and a set of 18 cylindrical PVDF membranes ( MWCO ∼ 100 kDa). For the production of the whey powder, two drying methods were compared: spray and freeze drying. All combinations lead to powder with high total protein content and with a notable content in these two bioactive proteins. However, cylindrical membranes (at a temperature of 20°C and a transmembrane pressure of 4 bar) in combination with freeze drying resulted in the highest yield from whey into Lf and IgG and excellent sensory characteristics. Practical Applications Whey powder enriched in the multifunctional proteins lactoferrin and immunoglobulin G have very large potential both as nutrition additives and for pharmaceutical purposes. The systematic study of the parameters affecting all unit operations involved leads to the most efficient and cheapest production. In order to achieve this, the methodology was kept as simple and low cost as possible. This way, a strong tool could be created for the utilization of the cheese-making by-product whey, which still causes large environmental problems. [ABSTRACT FROM AUTHOR]

Summary: Mass vaccination of the global population against SARS‐CoV‐2 will, we hope, turn the tide against this devastating pandemic. To complement vaccinations, better tools are needed to enable viral infections and immunological protection to be monitored. Accurate tools provide sound data for informed decision‐making at many levels, from personal to governmental. The measurement of viral RNA is currently routinely used to detect active infections, but only gives a positive result during infection and is unable to reveal historic infections. Tests involving a detection of SARS‐CoV‐2‐specific antibodies can reveal prior exposures to virus and can measure anti‐viral immune responses induced after natural infection or after vaccination. They may eventually also be used to predict an individual's likelihood of becoming re‐infected. Here, we report on the development of a sensitive ELISA technique to detect multiple isotypes of antibodies against the spike glycoprotein, in samples of both serum and saliva. This paper provides an important step towards understanding the immune response to SARS‐CoV‐2 and may therefore eventually help us to effectively control it. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tournier et al and Demarzo et al papers. To view these articles, visit https://doi.org/10.1111/apt.16333 and https://doi.org/10.1111/apt.16494 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tournier et al and Roblin et al papers. To view these articles, visit https://doi.org/10.1111/apt.16333 and https://doi.org/10.1111/apt.16501 [ABSTRACT FROM AUTHOR]

The article discusses the relationship between antibody specificities and efficacy of rituximab in patients with primary immune thrombocytopenia (ITP). The authors discovered that patients with anti-GPIIb/IIIa autoantibodies responded more to rituximab therapy. Autoantibody specificity was found before rituximab therapy using modified monoclonal antibody immobilization of platelet antigen assay.

LINKED CONTENT This article is linked to Lechtman et al and Ben Tov papers. To view these articles, visit https://doi.org/10.1111/apt.16282 and https://doi.org/10.1111/apt.16343 [ABSTRACT FROM AUTHOR]

Intravenous immune globulin (IVIG) was developed initially as an immunoglobulin replacement therapy for primary humoral immunodeficiency, but is now widely used in the treatment of autoinflammatory and autoimmune pathologies. In a small number of patients, hemolytic sequelae have been observed after IVIG administration. The lack of a simple one-to-one correlation between measurable hemagglutinins and hemolysis has led to complicated hypotheses involving coincident necessary variables (e.g., a two-hit hypothesis) and also to the positing of causal factors other than hemagglutinins. One such hypothesis is that immune complexes (ICs) contained within IVIG lead to hemolysis. IVIG-mediated hemolysis was addressed at a recent meeting sponsored by the Food and Drug Administration; the Plasma Protein Therapeutics Association; and the National Heart, Lung, and Blood Institute. The primary literature was reviewed at this meeting followed by detailed discussion. Participants concluded that there is both a theoretical basis by which ICs could contribute to hemolysis after IVIG administration and some published data in support of such a possibility. However, the reported data contain substantial caveats, and the existing evidence does not rise to a level sufficient to either confirm or reject a role for ICs. More detailed and focused human studies will be required to further assess the potential role of ICs in IVIG induced hemolysis. This paper summarizes the relevant literature and expands upon the conclusions of this workshop. [ABSTRACT FROM AUTHOR]

Pathogenic yeast forms are commonly associated with invasive fungal disease in the immunocompromised host, including patients with haematological malignancies and patients of haemopoietic stem cell transplants. Yeasts include the C andida spp., C ryptococcus spp., P neumocystis jirovecii and some lesser-known pathogens. Candida species remain the most common cause of invasive yeast infections (and the most common human pathogenic fungi). These guidelines present evidence-based recommendations for the antifungal management of established, invasive yeast infections in adult and paediatric patients in the haematology/oncology setting. Consideration is also given to the critically ill patient in intensive care units, including the neonatal intensive care unit. Evidence for 'pre-emptive' or 'diagnostic-driven antifungal therapy' is also discussed. For the purposes of this paper, invasive yeast diseases are categorised under the headings of invasive candidiasis, cryptococcosis and uncommon yeast infections. Specific recommendations for the management of P neumocystis jirovecii are presented in an accompanying article (see consensus guidelines by Cooley et al. appearing elsewhere in this supplement). [ABSTRACT FROM AUTHOR]

BACKGROUND This paper considers a real-world optimization problem involving the identification of cost-effective equipment sizing strategies for the sequence of chromatography steps employed to purify biopharmaceuticals. Tackling this problem requires solving a combinatorial optimization problem subject to multiple constraints, uncertain parameters, and time-consuming fitness evaluations. RESULTS An industrially-relevant case study is used to illustrate that evolutionary algorithms can identify chromatography sizing strategies with significant improvements in performance criteria related to process cost, time and product waste over the base case. The results demonstrate also that evolutionary algorithms perform best when infeasible solutions are repaired intelligently, the population size is set appropriately, and elitism is combined with a low number of Monte Carlo trials (needed to account for uncertainty). Adopting this setup turns out to be more important for scenarios where less time is available for the purification process. Finally, a data-visualization tool is employed to illustrate how user preferences can be accounted for when it comes to selecting a sizing strategy to be implemented in a real industrial setting. CONCLUSION This work demonstrates that closed-loop evolutionary optimization, when tuned properly and combined with a detailed manufacturing cost model, acts as a powerful decisional tool for the identification of cost-effective purification strategies. © 2013 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin therapy including intravenous immunoglobulin (IVIg) has been used as an effective treatment for autoimmune/inflammatory conditions with few side effects. However, high-dose IVIg (1-2 g/kg) has been recognized as a cause of hemolytic anemia in non-blood group O patients. Hemolysis when observed has been due to anti-A/anti-B isoagglutinins contained in the IVIg. Recently, an isoagglutinin-reduced IVIg, whereby the anti-A and anti-B titers have been reduced by immunoaffinity chromatography, has been introduced; however, whether this new product is as efficacious as nonreduced immunoglobulin (Ig) or will result in less IVIg-associated hemolysis has not been resolved.Study Design and Methods: We used in vitro phagocytosis by monocytes and proinflammatory/anti-inflammatory macrophages, with isoagglutinin-reduced and -nonreduced Ig opsonized group A1 , B, and A1 B red blood cells, to estimate clinical significance of the IgG isoagglutinins. We also used immune thrombocytopenia (ITP) and rheumatoid arthritis (RA) mouse models to examine the in vivo efficacy of isoagglutinin-reduced versus -nonreduced Ig on the amelioration of the diseases.Results: In contrast to nonreduced Ig, phagocytosis was largely absent when isoagglutinin-reduced Ig was used at a concentration equivalent to a patient receiving 2 g/kg. The in vivo efficacy of isoagglutinin-reduced versus nonreduced Ig on the amelioration of experimental ITP and RA was similar, indicating no loss of efficacy due to the chromatographic removal of isoagglutinins.Conclusion: Isoagglutinin-reduced Ig should have efficacy similar to nonreduced Ig and result in less IVIg-associated hemolysis. [ABSTRACT FROM AUTHOR]

Background: CD38 has been established as an important therapeutic target for multiple myeloma (MM), for which two CD38 antibodies are currently approved—daratumumab and isatuximab. CD38 is an ectoenzyme that degrades NAD and its precursors and is involved in the production of adenosine and other metabolites. Aim: Among the various mechanisms by which CD38 antibodies can induce MM cell death is immunomodulation, including multiple pathways for CD38‐mediated T‐cell activation. Patients who respond to anti‐CD38 targeting treatment experience more marked changes in T‐cell expansion, activity, and clonality than nonresponders. Implications: Resistance mechanisms that undermine the immunomodulatory effects of CD38‐targeting therapies can be tumor intrinsic, such as the downregulation of CD38 surface expression and expression of complement inhibitor proteins, and immune microenvironment‐related, such as changes to the natural killer (NK) cell numbers and function in the bone marrow niche. There are numerous strategies to overcome this resistance, which include identifying and targeting other therapeutic targets involved in, for example, adenosine production, the activation of NK cells or monocytes through immunomodulatory drugs and their combination with elotuzumab, or with bispecific T‐cell engagers. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the causal agent for coronavirus disease 2019 (COVID‐19). Although vaccines have helped to prevent uncontrolled viral spreading, our understanding of the fundamental biology of SARS‐CoV‐2 infection remains insufficient, which hinders effective therapeutic development. Here, we found that Apolipoprotein E (ApoE), a lipid binding protein, is hijacked by SARS‐CoV‐2 for infection. Preincubation of SARS‐CoV‐2 with a neutralizing antibody specific to ApoE led to inhibition of SARS‐CoV‐2 infection. The ApoE neutralizing antibody efficiently blocked SARS‐CoV‐2 infection of human iPSC‐derived astrocytes and air–liquid interface organoid models in addition to human ACE2‐expressing HEK293T cells and Calu‐3 lung cells. ApoE mediates SARS‐CoV‐2 entry through binding to its cellular receptors such as the low density lipoprotein receptor (LDLR). LDLR knockout or ApoE mutations at the receptor binding domain or an ApoE mimetic peptide reduced SARS‐CoV‐2 infection. Furthermore, we detected strong membrane LDLR expression on SARS‐CoV‐2 Spike‐positive cells in human lung tissues, whereas no or low ACE2 expression was detected. This study provides a new paradigm for SARS‐CoV‐2 cellular entry through binding of ApoE on the lipoviral particles to host cell receptor(s). Moreover, this study suggests that ApoE neutralizing antibodies are promising antiviral therapies for COVID‐19 by blocking entry of both parental virus and variants of concern. [ABSTRACT FROM AUTHOR]

Aims: Agonistic antibodies against neurohumoral receptors can induce cardio‐noxious effects by altering the baseline receptor activity. To estimate the prevalence of autoantibodies directed against the beta‐1 receptor (b1‐AAB) in patients admitted to the hospital for acute heart failure (HF) at (i) baseline and (ii) after 6 months of follow‐up (F6) and (iii) after another 12 months of follow‐up (i.e. 18 months after index hospitalization), to estimate their prognostic impact on clinical outcome (death or first hospitalization for HF). Methods and results: In 47 patients, b1‐AAB were serially determined in serum samples collected at index hospitalization and at 6 months of follow‐up (F6) with a flow cytometry‐based assay: median age 71 years (quartiles 60, 80), 23 (49%) women, 24 (51%) HF with preserved ejection fraction. Beta1‐AAB were detected in three subjects at index hospitalization (6%), and in eight subjects at F6 (17%). There were no differences apparent between patients with and without b1‐AAB at F6 with regard to age, sex, type, duration, or main cause of HF. During the 12 month period following F6 (i.e. up to month 18), eight events occurred. Event‐free survival was associated with prevalence of b1‐AAB at F6. Compared with patients without b1‐AAB at F6, age‐adjusted Cox regression indicated a higher event risk in patients harbouring b1‐AAB, with a hazard ratio of 8.96 (95% confidence interval 1.81–44.50, P = 0.007). Conclusions: Our results suggest a possible adverse prognostic relevance of b1‐AAB in patients with acute HF, but this observation needs to be confirmed in larger patient collectives. [ABSTRACT FROM AUTHOR]

Combinational immunotherapy of dendritic cell (DC) vaccines and anti‐programmed cell death protein 1 antibodies (aPD1) has been regarded as a promising strategy for cancer treatment because it not only induces tumor‐specific T cell immune responses, but also prevents failure of T cell functions by the immune suppressive milieu of tumors. Microneedles have emerged as an innovative platform for efficient transdermal immunotherapies. However, co‐delivery of DC vaccines and aPD1 via microneedles has not been studied since conventional microneedle platforms are unsuitable for fragile therapeutics like living cells and antibodies. This study employs our newly invented cryomicroneedles (cryoMNs) to co‐deliver DC vaccines and aPD1 for the combinational immunotherapy. CryoMNs are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre‐suspended DCs and aPD1, which are further integrated with a homemade handle for convenient application. The viability of DCs in cryoMNs remains above 85%. CryoMNs are mechanically strong enough to insert into porcine and mouse skin, successfully releasing DCs and aPD1 inside skin tissue after melting. Co‐delivery of ovalbumin (OVA)‐pulsed DCs (OVA‐DCs) and aPD1 via cryoMNs induced higher antigen‐specific cellular immune responses compared with the mono‐delivery of OVA‐DCs or aPD1. Finally, administration with cryoMNs co‐encapsulated with OVA‐DCs and aPD1 increases the infiltration of effector T cells in the tumor, resulting in stronger anti‐tumor therapeutic efficacy in both prophylactic and therapeutic melanoma models compared with administration with cryoMNs loaded with OVA‐DCs or aPD1. This study demonstrates the great potential of cryoMNs as a co‐delivery system of therapeutic cells and biomacromolecules for combinational therapies. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that various sphingolipids and glycosphingolipids can act as mediators for inflammation or signaling molecules in the nervous system. In this article, we explore the molecular basis of a new neuroinflammatory disorder called encephalomyeloradiculoneuropathy (EMRN), which affects the brain, spinal cord, and peripheral nerves; in particular, we discuss whether glycolipid and sphingolipid dysmetabolism is present in patients with this disorder. This review will focus on the pathognomonic significance of sphingolipid and glycolipid dysmetabolism for the development of EMRN and the possible involvement of inflammation in the nervous system. [ABSTRACT FROM AUTHOR]

Background: We sought to estimate SARS‐CoV‐2 antibody seroprevalence within representative samples of the Kenyan population during the third year of the COVID‐19 pandemic and the second year of COVID‐19 vaccine use. Methods: We conducted cross‐sectional serosurveys among randomly selected, age‐stratified samples of Health and Demographic Surveillance System (HDSS) residents in Kilifi and Nairobi. Anti‐spike (anti‐S) immunoglobulin G (IgG) serostatus was measured using a validated in‐house ELISA and antibody concentrations estimated with reference to the WHO International Standard for anti‐SARS‐CoV‐2 immunoglobulin. Results: HDSS residents were sampled in February–June 2022 (Kilifi HDSS N = 852; Nairobi Urban HDSS N = 851) and in August–December 2022 (N = 850 for both sites). Population‐weighted coverage for ≥1 doses of COVID‐19 vaccine were 11.1% (9.1–13.2%) among Kilifi HDSS residents by November 2022 and 34.2% (30.7–37.6%) among Nairobi Urban HDSS residents by December 2022. Population‐weighted anti‐S IgG seroprevalence among Kilifi HDSS residents increased from 69.1% (65.8–72.3%) by May 2022 to 77.4% (74.4–80.2%) by November 2022. Within the Nairobi Urban HDSS, seroprevalence by June 2022 was 88.5% (86.1–90.6%), comparable with seroprevalence by December 2022 (92.2%; 90.2–93.9%). For both surveys, seroprevalence was significantly lower among Kilifi HDSS residents than among Nairobi Urban HDSS residents, as were antibody concentrations (p < 0.001). Conclusion: More than 70% of Kilifi residents and 90% of Nairobi residents were seropositive for anti‐S IgG by the end of 2022. There is a potential immunity gap in rural Kenya; implementation of interventions to improve COVID‐19 vaccine uptake among sub‐groups at increased risk of severe COVID‐19 in rural settings is recommended. [ABSTRACT FROM AUTHOR]

Changes in the risk of exposure to infectious disease agents can be tracked through variations in antibody prevalence in vertebrate host populations. However, information on the temporal dynamics of the immune status of individuals is critical. If antibody levels persist a long time after exposure to an infectious agent, they could enable the efficient detection of the past circulation of the agent; if they persist only a short time, they could provide snap shots of recent exposure of sampled hosts. Here, we explored the temporal dynamics of seropositivity against Lyme disease agent Borrelia burgdorferi sensu lato (Bbsl) in individuals of a widespread medium‐sized mammal species, the roe deer (Capreolus capreolus), in France. Using a modified commercially available immunoassay we tested 1554 blood samples obtained in two wild deer populations monitored from 2010 to 2020. Using multi‐event capture‐mark‐recapture models, we estimated yearly population‐, age‐, and sex‐specific rates of seroconversion and seroreversion after accounting for imperfect detection. The yearly seroconversion rates indicated a higher level of exposure in early (2010–2013) than in late years (2014–2019) to infected tick bites in both populations, without any detectable influence of sex or age. The relatively high rates of seroreversion indicated a short‐term persistence of antibody levels against Bbsl in roe deer. This was confirmed by the analysis of samples collected on a set of captive individuals that were resampled several times a few weeks apart. Our findings show the potential usefulness of deer as a sentinel for tracking the risk of exposure to Lyme disease Bbsl, although further investigation on the details of the antibody response to Bbsl in this incompetent host would be useful. Our study also highlights the value of combining long‐term capture‐mark‐recapture sampling and short‐time analyses of serological data for wildlife populations exposed to infectious agents of relevance to wildlife epidemiology and human health. [ABSTRACT FROM AUTHOR]

Background: Sarajevo Canton in the Federation of Bosnia and Herzegovina has recorded several waves of high SARS‐CoV‐2 transmission and has struggled to reach adequate vaccination coverage. We describe the evolution of infection‐ and vaccine‐induced SARS‐CoV‐2 antibody response and persistence. Methods: We conducted repeated cross‐sectional analyses of blood donors aged 18–65 years in Sarajevo Canton in November–December 2020 and 2021. We analyzed serum samples for anti‐nucleocapsid (anti‐N) and anti‐spike (anti‐S) antibodies. To assess immune durability, we conducted longitudinal analyses of seropositive participants at 6 and 12 months. Results: One thousand fifteen participants were included in Phase 1 (November–December 2020) and 1152 in Phase 2 (November–December 2021). Seroprevalence increased significantly from 19.2% (95% CI: 17.2%–21.4%) in Phase 1 to 91.6% (95% CI: 89.8%–93.1%) in Phase 2. Anti‐S IgG titers were significantly higher among vaccinated (58.5%) than unvaccinated infected participants across vaccine products (p < 0.001), though highest among those who received an mRNA vaccine. At 6 months, 78/82 (95.1%) participants maintained anti‐spike seropositivity; at 12 months, 58/58 (100.0%) participants were seropositive, and 33 (56.9%) had completed the primary vaccine series within 6 months. Among 11 unvaccinated participants who were not re‐infected at 12 months, anti‐S IgG declined from median 770.1 (IQR 615.0–1321.7) to 290.8 (IQR 175.7–400.3). Anti‐N IgG antibodies waned earlier, from 35.4% seropositive at 6 months to 24.1% at 12 months. Conclusions: SARS‐CoV‐2 seroprevalence increased significantly over 12 months from end of 2020 to end of 2021. Although individuals with previous infection may have residual protection, COVID‐19 vaccination is vital to strengthening population immunity. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Strik et al and Strik, D'Heans papers. To view these articles visit https://doi.org/10.1111/apt.13994 and https://doi.org/10.1111/apt.14071. [ABSTRACT FROM AUTHOR]

W. K. Yong and D. D. Heath published in 1979 a seminal paper in the first issue of Parasite Immunology describing their efforts to determine whether the arc 5 precipitin band, formed when test human serum is reacted against electrophoresed hydatid cyst fluid antigen, would be a suitable immunodiagnostic test for the identification of sheep infected with Echinococcus granulosus. Although they found antibodies to arc 5 in the sera of hydatid-infected sheep, the sera of some sheep harbouring Taenia ovis and T. hydatigena also precipitated the hydatid cyst fluid arc 5 antigen, so they concluded arc 5 antibodies were not suitable for the specific immunodiagnosis of E. granulosus infection in sheep in New Zealand. Subsequent work has shown that the existence of multiple infections with different taeniid species, antigenic cross-reactivity between these related parasites and the low level of specific antibody response to infection continue to hinder efforts to improve the diagnosis of hydatid infection in sheep and other natural intermediate hosts, thereby preventing the development of any practical test. In particular, the poor antibody response of ruminants to naturally acquired hydatid infection may prove an insurmountable barrier in future efforts to develop a reliable and accurate immunological test. [ABSTRACT FROM AUTHOR]

Glycomimetic molecules can be used to antagonize the action of carbohydrate-binding proteins (lectins) involved in biological processes of high relevance for human and plant disease. In this paper we describe the derivatization with appropriate linkers of a previously described glycomimetic containing an α-fucosyl amide anchor that is known to act as antagonist of the dendritic cell lectin DC-SIGN. Key steps of the functionalization were the stereoselective epoxidation of an intermediate β-amino-cyclohexene-carboxylic acid derivative, followed by regioselective opening with 2-chloroethanol. Introduction of the linker does not alter the DC-SIGN binding properties of the molecule, as shown by Surface Plasmon Resonance and NMR studies. Whereas the fucose-based anchor allows the mimic to interact efficiently with fucose-binding lectins, the linker could also be exploited for the synthesis of glycodendrimers, as well as for the study of ligand interactions with commercially available lectins by array technology. In particular, a tetravalent fucosylated dendrimer was obtained that displayed a low-micromolar range of activity against DC-SIGN. Additionally, screening of the ligand against lectins with common fucose specificity in an array format allowed the lectin from the bacterium Ralstonia solanacearum (RSL) to be identified as a potential target protein and suggested that even simple glycomimetic structures can attain a significant amount of selectivity among lectins with analogous specificity. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Wunschi et al and Tornai & Papp papers. To view these articles, visit https://doi.org/10.1111/apt.16153 and https://doi.org/10.1111/apt.16201 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Wunschi et al and Wunsch & Milkiewicz papers. To view these articles, visit https://doi.org/10.1111/apt.16153 and https://doi.org/10.1111/apt.16211 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Nice et al paper. To view these articles, visit https://doi.org/10.1111/apt.16135 [ABSTRACT FROM AUTHOR]