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Omicron BA.1 variant can readily infect people with vaccine-induced or naturally acquired SARS-CoV-2 immunity facilitated by escape from neutralizing antibodies. In contrast, T-cell reactivity against the Omicron BA.1 variant seems relatively well preserved. Here, we studied the preexisting T cells elicited by either vaccination with the mRNA-based BNT162b2 vaccine or by natural infection with ancestral SARS-CoV-2 for their cross-reactive potential to 20 selected CD4+ T-cell epitopes of spike-protein-harboring Omicron BA.1 mutations. Although the overall memory CD4+ T-cell responses primed by the ancestral spike protein was still preserved generally, we show here that there is also a clear loss of memory CD4+ T-cell cross-reactivity to immunodominant epitopes across the spike protein due to Omicron BA.1 mutations. Complete or partial loss of preexisting T-cell responsiveness was observed against 60% of 20 nonconserved CD4+ T-cell epitopes predicted to be presented by a broad set of common HLA class II alleles. Monitoring such mutations in circulating strains helps predict which virus variants may escape previously induced cellular immunity and could be of concern. [ABSTRACT FROM AUTHOR]

Antibodies to the foot-and-mouth disease virus (FMDV) capsid induced by infection or vaccination can provide serotype-specific protection and be measured using virus neutralization tests and viral structural-protein (SP-)ELISAs. Separate tests are needed for each serotype, but cross-serotype reactions complicate serotyping. In this study, inter-serotypic responses were quantified for five SP-ELISA formats by testing 294 monovalent mainly bovine sera collected following infection, vaccination, or vaccination and infection with one of five serotypes of FMDV. Over half of the samples, representing all three immunization categories, scored positive for at least one heterologous serotype and some scored positive for all serotypes tested. A comparative approach to identifying the strongest reaction amongst serotypes O, A and Asia 1 improved the accuracy of serotyping to 73–100% depending on the serotype and test system, but this method will be undermined where animals have been infected and/or vaccinated with multiple FMDV serotypes. Preliminary studies with stabilized recombinant capsid antigens of serotypes O and A that do not expose internal epitopes showed reduced cross-reactivity, supporting the hypothesis that capsid integrity can affect the serotype-specificity of the SP-ELISAs. The residual cross-reactivity associated with capsid surface epitopes was consistent with the evidence of cross-serotype virus neutralization. [ABSTRACT FROM AUTHOR]

Ephrin-B1,-B2 and -B3 proteins share a high degree of sequence similarity. Investigation of these proteins as putative prognostic markers in human cancers including oral squamous cell carcinoma (OSCC) has been limited by challenges in generating specific antibodies against them. The current study examined the reactivity of a polyclonal anti-human ephrin-B2 antibody (HPA008999) against ephrin-B proteins and investigated the prognostic significance of immunoreactivity of the same antibody at different intra-tumor sites in OSCC specimens. By amino acid sequence comparison, immunocytochemistry and Western blot analysis on cell lysates and precipitates from HEK-293T cells transfected with EFNB1, EFNB2, or EFNB3 expression constructs, we demonstrated that HPA008999 reacted to all ephrin-B proteins. Using immunohistochemistry (IHC) with the HPA008999 antibody in a cohort (n = 131) of OSCC, we showed high immunoreactivity at the tumor center, but not at the tumor invading front, was significantly associated with worse 5-year overall survival probabilities. In conclusion, the HPA008999 antibody reacted to all ephrin-B proteins and the immunoreactivity at the tumor center might be useful as a prognostic marker in OSCC. These data underscore the need for the investigation of antibodies for cross-reactivity to similar protein members for obtaining reliable and meaningful results in IHC based biomarker studies. [ABSTRACT FROM AUTHOR]

Background: Oral immunotherapy (OIT) is a treatment option for patients with milk, egg, and peanut allergy, but data on the efficacy and safety of cashew OIT are limited. Methods: A cohort of 50 cashew‐allergic patients aged ≥4 years, who were consecutively enrolled into cashew OIT (target dose 4000 mg protein) between 4/2016 and 12/2019. Fifteen cashew‐allergic patients who continued cashew elimination served as observational controls. Co‐allergy to pistachio and walnut was determined. Full desensitization rate and associated immunological changes in both groups were compared. Patients fully desensitized to cashew were instructed to consume a dose of 1200 mg cashew protein for 6 months and were then challenged to a full dose. Patients with co‐allergy to pistachio or walnut were challenged to the respective nut. Results: Forty‐four of 50 OIT‐treated patients (88%) compared to 0% in controls tolerated a dose of 4000 mg cashew protein at the end of the study (odds ratio 8.3, 95% CI 3.9–17.7, p < 0.001). An additional three patients were desensitized to 1200 mg cashew protein, and three patients stopped treatment. Three patients (6%) were treated with injectable epinephrine for home reactions. Desensitized patients had decreased SPT, sIgE, basophil reactivity, and increased sIgG4, following treatment. Following cashew desensitization, all pistachio (n = 35) and four of eight walnut co‐allergic patients were cross‐desensitized to the respective nut. All (n = 44) patients consuming a low cashew dose for ≥6 months following desensitization passed a full‐dose cashew OFC. Conclusions: Cashew OIT desensitizes most cashew‐allergic patients and cross‐desensitizes to pistachio. Safety is similar to OIT for other foods. [ABSTRACT FROM AUTHOR]

Beta-lactam antibiotics are the most commonly reported drug allergy in adults and children. More than 95% of those with reported allergy labels to beta lactams are not confirmed when subjected to allergy testing. Beta lactam antibiotics are associated with a wide spectrum of immediate and delayed drug hypersensitivity reactions. The latency period to symptoms and clinical presentation aids in the causality assessment. Risk stratification based on diagnosis and timing then allows for appropriate management and evaluation. Skin prick testing, intradermal testing and oral challenge are well established for evaluation of immediate reactions. Delayed intradermal testing, patch testing and oral challenge can also be considered for evaluation of mild to moderate delayed reactions. Cross-reactivity between beta-lactams appears to be driven most commonly by a shared R1 side-chain. Standardized algorithms, protocols and pathways are needed for widespread implementation of a pragmatic and effective approach to patients reporting beta lactam allergy. [ABSTRACT FROM AUTHOR]

(1) Background: alpha-gal syndrome (AGS) is a serious, potentially life-threatening allergic reaction. This is a type of food allergy to red meat and other mammalian products (e.g., gelatin). In Poland, this problem seems to be rare or, more likely, very underdiagnosed. The diagnosis of AGS is difficult. It seems that the knowledge about this syndrome is insufficient. There are no effective diagnostic tools able to clearly diagnose this cross-reactive allergy. This paper presents the clinical application of a non-standard method in the diagnosis of a cross-reactive allergy using the example of AGS. (2) Methods: standard tests for in vitro allergy diagnostics and the non-standard ImmunoCAP inhibition test(IT) were carried out for serum collected from a patient with a red meat allergy. (3) Results: the serum concentration of anti-α-Gal IgE was very high (302 kUA/L), and IgE antibodies toanti-mammalian-meat allergens were found. The level of IgE antibodies to mammalian meat allergens decreased after blocking on α-GAL-CAP. The concentration of anti-α-Gal IgE decreased after blocking on CAPs coated with various mammalian meat allergens. Blocking with allergens of poultry meat did not affect the concentration of anti-α-Gal IgE. (4) Conclusions: the ImmunoCAP ITseems to be a useful tool in the diagnosis of cross-reactive allergies. Based on their clinical history and test results, the patient was diagnosed with AGS caused by a primary sensitization to α-Gal after a tick bite. This is the second case of AGS described in Poland and the first in Pomerania.

Despite the global interest and the unprecedented number of scientific studies triggered by the COVID-19 pandemic, few data are available from developing and low-income countries. In these regions, communities live under the threat of various transmissible diseases aside from COVID-19, including malaria. This study aims to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroreactivity of antibodies from COVID-19 and pre-COVID-19 samples of individuals in Mali (West Africa). Blood samples from COVID-19 patients (n = 266) at Bamako Dermatology Hospital (HDB) and pre-COVID-19 donors (n = 283) from a previous malaria survey conducted in Dangassa village were tested by ELISA to assess IgG antibodies specific to the full-length spike (S) protein, the receptor-binding domain (RBD), and the receptor-binding motif (RBM436–507). Study participants were categorized by age, gender, treatment duration for COVID-19, and comorbidities. In addition, the cross-seroreactivity of samples from pre-COVID-19, malaria-positive patients against the three antigens was assessed. Recognition of the SARS-CoV-2 proteins by sera from COVID-19 patients was 80.5% for S, 71.1% for RBD, and 31.9% for RBM (p < 0.001). While antibody responses to S and RBD tended to be age-dependent, responses to RBM were not. Responses were not gender-dependent for any of the antigens. Higher antibody levels to S, RBD, and RBM at hospital entry were associated with shorter treatment durations, particularly for RBD (p < 0.01). In contrast, higher body weights negatively influenced the anti-S antibody response, and asthma and diabetes weakened the anti-RBM antibody responses. Although lower, a significant cross-reactive antibody response to S (21.9%), RBD (6.7%), and RBM (8.8%) was detected in the pre-COVID-19 and malaria samples. Cross-reactive antibody responses to RBM were mostly associated (p < 0.01) with the absence of current Plasmodium falciparum infection, warranting further study. [ABSTRACT FROM AUTHOR]

Cryptococcus is an opportunistic pathogenic fungus and is the major cause of fungal meningitis. The cryptococcal antigen (CrAg) lateral flow assay (LFA) is an immunochromatographic test system that has simplified diagnosis as a point-of-care test. In this study, we evaluated the diagnostic performance of Cryptococcal capsular polysaccharide detection FungiXpert (Genobio Pharmaceutical, Tianjin, China) using serum and cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcosis and investigated the cross-reaction of the assays to pathogenic fungi and bacterium by comparing it to the U.S. Food and Drug Administration (US FDA)-approved IMMY CrAg LFA. Eighty CSF and 119 serum/plasma samples from 158 patients were retrospectively collected to test for qualitative or semi-quantitative detection of CrAg. Cross-reaction of the assays was tested using 28 fungi and 1 bacterium. Compared to IMMY CrAg LFA, the FungiXpert LFA demonstrated 99.1% sensitivity and 98.9% specificity in the qualitative test. In the 96 semi-quantitative CrAg assay results, 39 (40.6%) test titers of FungiXpert LFA were 1–2 dilutions higher than those of IMMY CrAg LFA. The Intraclass Correlation Coefficient of the Semi-quantitative results of CrAg titer tests via the two assays was 0.976. Similar to IMMY CrAg LFA, FungiXpert LFA showed cross-reactivity with Trichosporon asahii. Compared with the IMMY CrAg LFA, the FungiXpert LFA showed an equal, yet, excellent performance. However, it is important to note that these two assays have potential cross-reactivity to T. asahii when diagnosing patients. FungiXpert LFA is a rapid screening method for the effective and practical diagnosis and treatment of cryptococcosis. Lay summary The FungiXpert LFA was developed to diagnose fungal meningitis caused by Cryptococcus yeasts, by using serum or cerebrospinal fluid. It was compared to an existing lateral flow assay (LFA). The FungiXpert LFA performed well in qualitative and semi-quantitative tests. [ABSTRACT FROM AUTHOR]

Genetically encoded photosensitizers are able to produce reactive oxygen species upon illumination and are exploited in a wide range of applications, especially in the medical field. In this work, we envisioned to further apply these genetically encoded photosensitizers for the light-dependent control of single enzymes in multi-step biocatalysis. One of the challenges in the application of several enzymes in a cascade is the unwanted crossreactivity of these biocatalysts on reaction intermediates when all enzymes are simultaneously present in the reaction. As one strategy to address this issue, we investigated whether the introduction of genetically encoded photosensitizers as fusion tags would allow the selective inactivation of enzymes after successful transformation by simply turning on light. We tested five different photosensitizers as molecular biological fusion tags to inactivate the pyruvate decarboxylase variant E469G/W543H from Acetobacter pasteurianus. Dimeric photosensitizer tags, like the flavin-binding fluorescent proteins from Bacillus subtilis and Pseudomonas putida showed the tendency to form insoluble protein aggregates in combination with the tetrameric carboligase. Enzyme activity was, to some extent, retained in these aggregates, but the handling of the insoluble aggregates proved to be unfeasible. Monomeric photosensitizer tags appeared to be much more suitable when fused to the tetrameric enzyme. In the dark, the singlet oxygen photosensitizing protein (SOPP3)-tagged carboligase retained 79% of its activity as compared to the unfused enzyme. Upon blue light exposure, the SOPP3 tag showed the best specific inactivation and enabled complete inactivation of the carboligase within 30 min. SOPP3 is thus seen as a promising photosensitizer tag to be applied in future multi-step enzyme cascades to overcome the challenge of cross-reactivity. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease of the central nervous system (CNS) with a high socioeconomic relevance. The pathophysiology of MS, which is both complex and incompletely understood, is believed to be influenced by various environmental determinants, including diet. Since the 1990s, a correlation between the consumption of bovine milk products and MS prevalence has been debated. Here, we show that C57BL/6 mice immunized with bovine casein developed severe spinal cord pathology, in particular, demyelination, which was associated with the deposition of immunoglobulin G. Furthermore, we observed binding of serum from casein-immunized mice to mouse oligodendrocytes in CNS tissue sections and in culture where casein-specific antibodies induced complement-dependent pathology. We subsequently identified myelin-associated glycoprotein (MAG) as a cross-reactive antigenic target. The results obtained from the mouse model were complemented by clinical data showing that serum samples from patients with MS contained significantly higher B cell and antibody reactivity to bovine casein than those from patients with other neurologic diseases. This reactivity correlated with the B cell response to a mixture of CNS antigens and could again be attributed to MAG reactivity. While we acknowledge disease heterogeneity among individuals with MS, we believe that consumption of cow’s milk in a subset of patients with MS who have experienced a previous loss of tolerance to bovine casein may aggravate the disease. Our data suggest that patients with antibodies to bovine casein might benefit from restricting dairy products from their diet. [ABSTRACT FROM AUTHOR]

In the context of HLA-DP-mismatched allogeneic stem cell transplantation, mismatched HLA-DP alleles can provoke profound allo-HLA-DP-specific immune responses from the donor T-cell repertoire leading to graft-versus-leukemia effect and/or graft-versus-host disease in the patient. The magnitude of allo-HLA-DP-specific immune responses has been shown to depend on the specific HLA-DP disparity between donor and patient and the immunogenicity of the mismatched HLA-DP allele(s). HLA-DP peptidome clustering (DPC) was developed to classify the HLA-DP molecules based on similarities and differences in their peptide-binding motifs. To investigate a possible categorization of HLA-DP molecules based on overlap of presented peptides, we identified and compared the peptidomes of the thirteen most frequently expressed HLA-DP molecules. Our categorization based on shared peptides was in line with the DPC classification. We found that the HLA-DP molecules within the previously defined groups DPC-1 or DPC-3 shared the largest numbers of presented peptides. However, the HLA-DP molecules in DPC-2 segregated into two subgroups based on the overlap in presented peptides. Besides overlap in presented peptides within the DPC groups, a substantial number of peptides was also found to be shared between HLA-DP molecules from different DPC groups, especially for groups DPC-1 and -2. The functional relevance of these findings was illustrated by demonstration of cross-reactivity of allo-HLA-DP-reactive T-cell clones not only against HLA-DP molecules within one DPC group, but also across different DPC groups. The promiscuity of peptides presented in various HLA-DP molecules and the cross-reactivity against different HLA-DP molecules demonstrate that these molecules cannot be strictly categorized in immunogenicity groups. [ABSTRACT FROM AUTHOR]

Sensitization to lipid transfer protein (LTP), the most frequent cause of food allergy in southern Europe, still shows several controversial, but also intriguing, aspects. Some of these include the degree of cross‐reactivity between LTPs from botanically distant sources, the definition of risk factors, the role of some cofactors, clinical outcomes, geographical differences and the identification of the primary sensitizer in different areas. This review article tries to analyse and comment on these aspects point by point suggesting some explanatory hypotheses with the final scope to stimulate critical thoughts and elicit the scientific discussion about this issue in the readership. [ABSTRACT FROM AUTHOR]

Background: Biology has entered the era of big data with the advent of high-throughput omics technologies. Biological databases provide public access to petabytes of data and information facilitating knowledge discovery. Over the years, sequence data of pathogens has seen a large increase in the number of records, given the relatively small genome size and their important role as infectious and symbiotic agents. Humans are host to numerous pathogenic diseases, such as that by viruses, many of which are responsible for high mortality and morbidity. The interaction between pathogens and humans over the evolutionary history has resulted in sharing of sequences, with important biological and evolutionary implications. Results: This study describes a large-scale, systematic bioinformatics approach for identification and characterization of shared sequences between the host and pathogen. An application of the approach is demonstrated through identification and characterization of the Flaviviridae-human share-ome. A total of 2430 nonamers represented the Flaviviridae-human share-ome with 100% identity. Although the share-ome represented a small fraction of the repertoire of Flaviviridae (~ 0.12%) and human (~ 0.013%) non-redundant nonamers, the 2430 shared nonamers mapped to 16,946 Flaviviridae and 7506 human non-redundant protein sequences. The shared nonamer sequences mapped to 125 species of Flaviviridae, including several with unclassified genus. The majority (~ 68%) of the shared sequences mapped to Hepacivirus C species; West Nile, dengue and Zika viruses of the Flavivirus genus accounted for ~ 11%, ~ 7%, and ~ 3%, respectively, of the Flaviviridae protein sequences (16,946) mapped by the share-ome. Further characterization of the share-ome provided important structural-functional insights to Flaviviridae-human interactions. Conclusion: Mapping of the host-pathogen share-ome has important implications for the design of vaccines and drugs, diagnostics, disease surveillance and the discovery of unknown, potential host-pathogen interactions. The generic workflow presented herein is potentially applicable to a variety of pathogens, such as of viral, bacterial or parasitic origin. [ABSTRACT FROM AUTHOR]

House dust mite (HDM) is a main perennial allergen causing allergic rhinitis (AR). It has been shown that HDM cross-reacts with a variety of other allergens. Presently, allergen-specific immunotherapy (AIT) is an effective way for management of mono-sensitized HDM+ AR patients. However, management approaches to polysensitized HDM-sensitized AR patients are not standardized yet. This article reviews the data available in the literature for cross-reactivity between HDM and inhalant or food allergens, the diagnosis of cross-reactivity in HDM-sensitized AR patients, and the effect of immunotherapy on cross-reactivity in HDM-sensitized AR patients; which may help to develop effective therapeutic strategies for management of polysensitized HDM-sensitized AR patients in the future. Pan-allergen proteins such as tropomyosin, arginine kinase (AK), glutathione S-transferase (GST), and hemocyanin are responsible for cross-reactivity between HDM and other allergens. To distinguish genuine or cross-reactive sensitization, molecular- or component-resolved diagnosis is suggested to apply in HDM-sensitized AR patients. The effect of HDM immunotherapy to treat the associated cross-reactivity in HDM-sensitized AR patients is still contradictory, and might be dependent on the degree of homology between two allergens. Furthermore, targeting tropomyosin might be a promising way to treat HDM patients with allergen cross-reactivity AIT: allergen-specific immunotherapy; AK: arginine kinase; AR: allergic rhinitis; CRD: component-resolved diagnostics; Der f: Dermatophagoides farina; Der p: Dermatophagoides pteronyssinus; EAACI: European Academy of Allergy and Clinical Immunology; GST: glutathione S-transferase; GWAS: genome-wide association study; HDM: house dust mite; IgE: immunoglobulin E; RAST: radioallergosorbent test; sIgE: specific IgE; SIT: specific immunotherapy; SCIT: subcutaneous immunotherapy; SLIT: sublingual immunotherapy; SPT: skin prick test [ABSTRACT FROM AUTHOR]

Background: The emergence and re-emergence of infectious diseases are a cause for worldwide concern. The introduction of Zika and Chikungunya diseases in the Americas has exposed unforeseen medical and logistical challenges for public health systems. Moreover, the lack of preventive measures and vaccination against known and emerging mosquito-transmitted pathogens, and the occurrence of unanticipated clinical complications, has had an enormous social and economic impact on the affected populations. In this study, we aimed to measure the seroprevalence of endemic and emerging viral pathogens in military personnel stationed in Manaus, Amazonas state. Methods: We measured the seropositivity of antibodies against 19 endemic and emerging viruses in a healthy military personnel group using a hemagglutination inhibition assay (HIA). Results: Overall, DENV positivity was 60.4%, and 30.9% of the individuals reacted against ZIKV. Also, 46.6%, 54.7%, 51.3% and 48.7% individuals reacted against West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilheus virus (ILHV) and Rocio virus (ROCV), respectively. Individuals with high DENV HIA titer reacted more frequently with ZIKV or WNV compared to those with low HIA titers. Observed cross-reactivity between Flaviviruses varied depending on the virus serogroup. Additionally, 0.6% and 0.3% individuals were seropositive for Oropouche virus (OROV) and Catu virus (CATUV) from the family Peribunyaviridae, respectively. All samples were negative for Eastern Equine Encephalitis virus (EEEV), Western Equine Encephalomyelitis virus (WEEV), Mayaro virus (MAYV), Mucambo virus (MUCV) and CHIKV from the family Togaviridae. Conclusions: A high proportion of individuals in our high-risk population (~ 60%) lacked antibodies against major endemic and emerging viruses, which makes them susceptible for further infections. Military personnel serving in the Amazon region could serve as sentinels to strengthen global infectious disease surveillance, particularly in remote areas. [ABSTRACT FROM AUTHOR]

Many applications of immunoassays involve the possible presence of structurally similar compounds that bind with antibodies, but with different affinities. In this regard, an important characteristic of an immunoassay is its cross-reactivity: the possibility of detecting various compounds in comparison with a certain standard. Based on cross-reactivity, analytical systems are assessed as either high-selective (responding strictly to a specific compound) or low-selective (responding to a number of similar compounds). The present study demonstrates that cross-reactivity is not an intrinsic characteristic of antibodies but can vary for different formats of competitive immunoassays using the same antibodies. Assays with sensitive detection of markers and, accordingly, implementation at low concentrations of antibodies and modified (competing) antigens are characterized by lower cross-reactivities and are, thus, more specific than assays requiring high concentrations of markers and interacting reagents. This effect was confirmed by both mathematical modeling and experimental comparison of an enzyme immunoassay and a fluorescence polarization immunoassay of sulfonamides and fluoroquinolones. Thus, shifting to lower concentrations of reagents decreases cross-reactivities by up to five-fold. Moreover, the cross-reactivities are changed even in the same assay format by varying the ratio of immunoreactants' concentrations and shifting from the kinetic or equilibrium mode of the antigen-antibody reaction. The described patterns demonstrate the possibility of modulating immunodetection selectivity without searching for new binding reactants. [ABSTRACT FROM AUTHOR]

Purpose of Review: The recent introduction of edible insects in Western countries has raised concerns about their safety in terms of allergenic reactions. The characterization of insect allergens, the sensitization and cross-reactivity mechanisms, and the effects of food processing represent crucial information for risk assessment. Recent Findings: Allergic reactions to different insects and cross-reactivity with crustacean and inhalant allergens have been described, with the identification of new IgE-binding proteins besides well-known pan-allergens. Depending on the route of sensitization, different potential allergens seem to be involved. Food processing may affect the solubility and the immunoreactivity of insect allergens, with results depending on species and type of proteins. Chemical/enzymatic hydrolysis, in some cases, abolishes immunoreactivity. Summary: More studies based on subjects with a confirmed insect allergy are necessary to identify major and minor allergens and the role of the route of sensitization. The effects of processing need to be further investigated to assess the risk associated with the ingestion of insect-containing food products. [ABSTRACT FROM AUTHOR]

Enterobacteriaceae are a large family of Gram‐negative bacteria that includes both commensals and opportunistic pathogens. The latter can cause severe nosocomial infections, with outbreaks of multi‐antibiotics resistant strains, thus being a major public health threat. In this study, we report that Enterobacteriaceae‐reactive memory Th cells were highly enriched in a CCR6+CXCR3+ Th1*/17 cell subset and produced IFN‐γ, IL‐17A, and IL‐22. This T cell subset was severely reduced in septic patients with K. pneumoniae bloodstream infection who also selectively lacked circulating K. pneumonie‐reactive T cells. By combining heterologous antigenic stimulation, single cell cloning and TCR Vβ sequencing, we demonstrate that a large fraction of memory Th cell clones was broadly cross‐reactive to several Enterobacteriaceae species. These cross‐reactive Th cell clones were expanded in vivo and a large fraction of them recognized the conserved outer membrane protein A antigen. Interestingly, Enterobacteriaceae broadly cross‐reactive T cells were also prominent among in vitro primed naïve T cells. Collectively, these data point to the existence of immunodominant T cell epitopes shared among different Enterobacteriaceae species and targeted by cross‐reactive T cells that are readily found in the pre‐immune repertoire and are clonally expanded in the memory repertoire. [ABSTRACT FROM AUTHOR]

While COVID-19 continues to spread across the globe, diligent efforts are made to understand its attributes and dynamics to help develop treatment and prevention measures. The paradox pertaining to children being the least affected by severe illness poses exciting opportunities to investigate potential protective factors. In this paper, we propose that childhood vaccination against pertussis (whooping cough) might play a non-specific protective role against COVID-19 through heterologous adaptive responses in this young population. Pertussis is a vaccine-preventable infectious disease of the respiratory tract and it shares many similarities with COVID-19 including transmission and clinical features. Although pertussis is caused by a bacterium (Bordetella pertussis) while COVID-19 is a viral infection (SARS-CoV-2), previous data showed that cross-reactivity and heterologous adaptive responses can be seen with unrelated agents of highly divergent groups, such as between bacteria and viruses. While we build the arguments of this hypothesis on theoretical and previous empirical evidence, we also outline suggested lines of research from different fields to test its credibility. Besides, we highlight some concerns that may arise when attempting to consider such an approach as a potential public health preventive intervention against COVID-19. [ABSTRACT FROM AUTHOR]

Unspecific antibody binding takes a significant toll on researchers in the form of both the economic burden and the disappointed hopes of promising new therapeutic targets. Despite recent initiatives promoting antibody validation, a uniform approach addressing this issue has not yet been developed. Here, we demonstrate that the anti-glucocorticoid receptor (GR) antibody clone 5E4 predominantly targets two different proteins of approximately the same size, namely AMP deaminase 2 (AMPD2) and transcription intermediary factor 1-beta (TRIM28). This paper is intended to generate awareness of unspecific binding of well-established reagents and advocate the use of more rigorous verification methods to improve antibody quality in the future.

Objectives: The emergence of a SARS‐CoV‐2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross‐neutralise against the G614 variant. Methods: Antibody profiling against the SARS‐CoV‐2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS‐CoV‐2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID‐19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). Results: Profiling of the anti‐SARS‐CoV‐2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. Conclusions: Cross‐reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS‐CoV‐2. More importantly, there should be negligible impact towards the efficacy of antibody‐based therapies and vaccines that are currently being developed. [ABSTRACT FROM AUTHOR]

The use of T cells reactive with intracellular tumor-associated or tumor-specific antigens has been a promising strategy for cancer immunotherapies in the past three decades, but the approach has been constrained by a limited understanding of the T cell receptor's (TCR) complex functions and specificities. Newer TCR and T cell-based approaches are in development, including engineered adoptive T cells with enhanced TCR affinities, TCR mimic antibodies, and T cell-redirecting bispecific agents. These new therapeutic modalities are exciting opportunities by which TCR recognition can be further exploited for therapeutic benefit. In this review we summarize the development of TCR-based therapeutic strategies and focus on balancing efficacy and potency versus specificity, and hence, possible toxicity, of these powerful therapeutic modalities. [ABSTRACT FROM AUTHOR]

β-Lactams which include penicillins, cephalosporins, carbapenems, and monobactams are the most common antibiotic classes reported to cause allergic reactions to drugs. This review is mainly about published studies assessing the cross-reactivity among β-lactams in penicillin- or cephalosporin-allergic subjects by carrying out diagnostic tests with alternative β-lactams and, if appropriate, graded challenges. Several studies demonstrated that cross-reactivity connected with the β-lactam ring, causing positive responses to allergy tests with all β-lactams, is infrequent in subjects with an IgE-mediated allergy and anecdotal in those with a T-cell-mediated allergy. Identities or similarities of β-lactam side-chain structures are mainly responsible for cross-reactivity among these antibiotics. For example, in aminopenicillin-allergic subjects, cross-reactivity with aminocephalosporins could possibly be over 30%. On the other hand, in a few prospective studies of penicillin-allergic individuals, less than 1% of cases show a cross-reactivity between penicillins and both aztreonam and carbapenems. Particular patterns of allergy-test positivity observed in some studies that assessed cross-reactivity among β-lactams seem to indicate that prior exposures may be responsible for coexisting sensitivities. Therefore, pre-treatment skin tests with the related β-lactams are suggested before administering them via graded challenges to β-lactam-allergic patients who need alternative β-lactams. [ABSTRACT FROM AUTHOR]

Background: Analysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Amoxicillin (AX) is the betalactam most often involved in immediate hypersensitivity reactions (IHRs), and cefadroxil (CX) the most likely cephalosporin to cross-react with AX, since they share the same R1 side chain, unlike cefuroxime (CO), with a structurally different R1. We aimed to analyse cross-reactivity with CX and CO in patients with confirmed IHRs to AX, including sIgE recognition to AX, CX, CO, and novel synthetic determinants of CX. Methods: Fifty-four patients with confirmed IHRs to AX based on skin test (ST) and/or drug provocation test (DPT) were included. Serum sIgE to AX and benzylpenicillin was determined by Radioallergosorbent test (RAST). Two potential determinants of CX, involving intact or modified R1 structure, with open betalactam ring, were synthesised and sIgE evaluated by RAST inhibition assay. Results: Tolerance to CX (Group A) was observed in 64.8% cases and cross-reactivity in 35.2% cases (Group B). Cross-reactivity with CO was only found in 1.8% cases from Group B. ST to CX showed a negative predictive value of 94.6%. RAST inhibition assays showed higher recognition to CX as well as to both synthetic determinants (66% of positive cases) in Group B. Conclusions: Cross-reactivity with CX in AX allergic patients is 35%, being ST not enough for prediction. R1, although critical for recognition, is not the unique factor. The synthetic determinants of CX, 1-(HOPhG-Ser-Bu) and 2-(pyrazinone) are promising tools for determining in vitro cross-reactivity to CX in AX allergic patients. [ABSTRACT FROM AUTHOR]

ABSTRACT In contrast to influenza virus vaccination, natural infection induces long-lived and relatively broad immune responses. However, many aspects of the antibody response to natural infection are not well understood. Here, we assessed the immune response after H1N1 influenza virus infection in children and adults in a Nicaraguan household transmission study using an influenza virus protein microarray (IVPM). This technology allows us to simultaneously measure IgG and IgA antibody responses to hemagglutinins of many different virus strains and subtypes quantitatively with a high throughput. We found that children under 6 years of age responded to natural infection with a relatively narrow response that targeted mostly the hemagglutinin of the strain that caused the infection. Adults, however, have a much broader response, including a boost in antibodies to many group 1 subtype hemagglutinins. Also, a strong recall response against historic H1 hemagglutinins that share the K133 epitope with the pandemic H1N1 virus was observed. Of note, some children, while responding narrowly within H1 and group 1 hemagglutinins, induced a boost to H3 and other group 2 hemagglutinins when infected with H1N1 when they had experienced an H3N2 infection earlier in life. This is an interesting phenomenon providing evidence for immune imprinting and a significant new insight which might be leveraged in future universal influenza virus vaccine strategies. Finally, preexisting immunity to pandemic H1 hemagglutinins was significantly associated with protection from infection in both children and adults. In adults, preexisting immunity to non-H1 group 1 hemagglutinins was also significantly associated with protection from infection. IMPORTANCE It is known since Thomas Francis, Jr. published his first paper on original antigenic sin in 1960 that the first infection(s) with influenza virus leaves a special immunological imprint which shapes immune responses to future infections with antigenically related influenza virus strains. Imprinting has been implicated in both protective effects as well as blunting of the immune response to vaccines. Despite the fact that this phenomenon was already described almost 60 years ago, we have very little detailed knowledge of the characteristics and breadth of the immune response to the first exposure(s) to influenza virus in life and how this compares to later exposure as adults. Here, we investigate these immune responses in detail using an influenza virus protein microarray. While our findings are mostly descriptive in nature and based on a small sample size, they provide a strong basis for future large-scale studies to better understand imprinting effects.

(B) D2: strong positive patch test reactions (++) to sesquiterpene lactone mix (SLM) 0.1% pet. on the previous positive patch tests sites of IBOA (no. 1 = 0.1%, no. 2 = 0.3%) on the right upper arm. Keywords: allergic contact dermatitis; case report; cosensitization; cross-reactivity; diabetes mellitus; FreeStyle Libre; glucose sensor; medical devices; re-test method; sesquiterpene lactones EN allergic contact dermatitis case report cosensitization cross-reactivity diabetes mellitus FreeStyle Libre glucose sensor medical devices re-test method sesquiterpene lactones 57 59 3 12/17/21 20220101 NES 220101 Patients with allergic contact dermatitis from the glucose sensor FreeStyle Libre (Abbott Diabetes Care, Witney, UK) are often (strongly) sensitized to isobornyl acrylate (IBOA).1,2 About 40% to 60% of these patients also have a concomitant positive patch test to the sesquiterpene lactone mix (SLM; 0.1% pet.), Unexpected positive patch test reactions to sesquiterpene lactones in patients sensitized to the glucose sensor FreeStyle libre. [Extracted from the article]

Dengue is one of the most frequently transmitted mosquito-borne diseases in the world, which creates a significant public health concern globally, especially in tropical and subtropical countries. It is estimated that more than 390 million people are infected with dengue virus each year and around 96 million develop clinical pathologies. Dengue infections are not only a health problem but also a substantial economic burden. To date, there are no effective antiviral therapies and there is only one licensed dengue vaccine that only demonstrated protection in the seropositive (Immune), naturally infected with dengue, but not dengue seronegative (Naïve) vaccines. In this review, we address several immune components and their interplay with the dengue virus. Additionally, we summarize the literature pertaining to current dengue vaccine development and advances. Moreover, we review some of the factors affecting vaccine responses, such as the pre-vaccination environment, and provide an overview of the significant challenges that face the development of an efficient/protective dengue vaccine including the presence of multiple serotypes, antibody-dependent enhancement (ADE), as well as cross-reactivity with other flaviviruses. Finally, we discuss targeting T follicular helper cells (Tfh), a significant cell population that is essential for the production of high-affinity antibodies, which might be one of the elements needed to be specifically targeted to enhance vaccine precision to dengue regardless of dengue serostatus. [ABSTRACT FROM AUTHOR]

Bioinformatic amino acid sequence searches are used, in part, to assess the potential allergenic risk of newly expressed proteins in genetically engineered crops. Previous work has demonstrated that the searches required by government regulatory agencies falsely implicate many proteins from rarely allergenic crops as an allergenic risk. However, many proteins are found in crops at concentrations that may be insufficient to cause allergy. Here we used a recently developed set of high-abundance non-allergenic proteins to determine the false-positive rates for several algorithms required by regulatory bodies, and also for an alternative 1:1 FASTA approach previously found to be equally sensitive to the official sliding-window method, but far more selective. The current investigation confirms these earlier findings while addressing dietary exposure. [ABSTRACT FROM AUTHOR]

Background: Ole e 7 is a nonspecific lipid transfer protein (nsLTP) from olive pollen, one of the main allergenic pollens worldwide. This allergenic nsLTP is responsible for severe symptoms in regions with high olive pollen exposure, where many Ole e 7‐sensitized patients exhibit a co‐sensitization to the peach nsLTP, Pru p 3. However, there is no evidence of cross‐reactivity, which explains this observed co‐sensitization. Therefore, the purpose of this study was to explore the relationship between Ole e 7 and Pru p 3. Methods: A total of 48 patients sensitized to Ole e 7 and/or Pru p 3 were included in the study. Specific IgE serum levels were measured by ImmunoCAP 250 and ELISA. Inhibition assays were performed to determine the existence of cross‐reactivity between both nsLTPs. Allergic response was analyzed ex vivo (basophil activation test) and in vitro (RBL‐2H3 mast cell model). Results: Common IgG and IgE epitopes were identified between both allergens. IgE‐binding inhibition was detected in Ole e 7–monosensitized patients using rPru p 3 as inhibitor, reaching inhibition values of 25 and 100%. Ex vivo and in vitro assays revealed a response against rPru p 3 in four (31%) Ole e 7–monosensitized patients. Conclusions: Our results suggest that Ole e 7 could play a new role as primary sensitizer in regions with high olive pollen exposure, leading to the peach nsLTP sensitization. This co‐sensitization process would occur because of the cross‐reactivity between Ole e 7 and Pru p 3 observed in some allergic patients. [ABSTRACT FROM AUTHOR]

Background and aims: Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti‐HEV IgM and IgG, and HEV‐RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti‐HEV serology. Methods: One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non‐AIH). Results: Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non‐AIH). Patients with acute AIH and positive anti‐HEV IgG were older (58 vs 40; P =.006), had higher IgG levels (27 g/dL vs 13 g/dL; P =.03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P =.045), and were more likely to have another autoimmune disease (60% vs 16%; P =.03). At the time of HEV testing, anti‐HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P =.009), ANA (1:160 vs 1:60; P =.026) and ASMA titres (1:80 vs 1:40; P =.021). Conclusion: Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross‐reactivity between HEV and liver antigens. [ABSTRACT FROM AUTHOR]

Background: Analysis of cross‐reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Amoxicillin (AX) is the betalactam most often involved in immediate hypersensitivity reactions (IHRs), and cefadroxil (CX) the most likely cephalosporin to cross‐react with AX, since they share the same R1 side chain, unlike cefuroxime (CO), with a structurally different R1. We aimed to analyse cross‐reactivity with CX and CO in patients with confirmed IHRs to AX, including sIgE recognition to AX, CX, CO, and novel synthetic determinants of CX. Methods: Fifty‐four patients with confirmed IHRs to AX based on skin test (ST) and/or drug provocation test (DPT) were included. Serum sIgE to AX and benzylpenicillin was determined by Radioallergosorbent test (RAST). Two potential determinants of CX, involving intact or modified R1 structure, with open betalactam ring, were synthesised and sIgE evaluated by RAST inhibition assay. Results: Tolerance to CX (Group A) was observed in 64.8% cases and cross‐reactivity in 35.2% cases (Group B). Cross‐reactivity with CO was only found in 1.8% cases from Group B. ST to CX showed a negative predictive value of 94.6%. RAST inhibition assays showed higher recognition to CX as well as to both synthetic determinants (66% of positive cases) in Group B. Conclusions: Cross‐reactivity with CX in AX allergic patients is 35%, being ST not enough for prediction. R1, although critical for recognition, is not the unique factor. The synthetic determinants of CX, 1 ‐(HOPhG‐Ser‐Bu) and 2 ‐(pyrazinone) are promising tools for determining in vitro cross‐reactivity to CX in AX allergic patients. [ABSTRACT FROM AUTHOR]