Evidence of taxonomic bias in public databases: The example of the genus Borrelia

The taxon names used in public databases are of critical importance in all areas of biology because they are needed for linking organisms to sequence data and other information. Since most users of taxonomic classifications may be unprepared for dealing with synonyms, the names that are preferred in such databases are of high impact. Using the genus Borrelia as an example, we here show how simplistic approaches for determining the preferred synonym may lead to biases regarding the preferences for taxonomic opinions. We highlight that in this and other cases where genera were split, for reverting to the previous “merged” genus it is neither possible nor necessary to generate validly published and legitimate names that are newer than those that were proposed as new combinations when the genus was split. The policy to always prefer the latest validly published name in a public database may thus render this database oblivious to reversals in taxonomic opinion. We emphasize that users of public databases should be aware of such potential shortcomings, and that curators of databases which provide nomenclatural information should be open-minded about taxonomic views expressed in the literature.     

Antigenic cartography using sera from sequence-confirmed SARS-CoV-2 variants of concern infections reveals antigenic divergence of Omicron

1. Download : Download high-res image (182KB)
2. Download : Download full-size image

     

High dose trivalent influenza vaccine compared to standard dose vaccine in patients with rheumatoid arthritis receiving TNF-alpha inhibitor therapy and healthy controls: Results of the DMID 10-0076 randomized clinical trial

IntroductionSubjects with rheumatoid arthritis (RA) receiving tumor necrosis factor-inhibiting (TNFi) therapies are at risk for severe influenza, and may respond less well to influenza vaccine. We examined the safety and immunogenicity of high dose influenza vaccine (HD) compared to standard dose vaccine (SD) in participants with RA receiving stable TNFi.MethodsA randomized, double-blinded, Phase II study was conducted in adults with RA receiving TNFi, and healthy, gender and age-matched control subjects. Participants were immunized with HD (Sanofi Pasteur Fluzone High Dose [60 mcg × 3 strains]) or SD (Sanofi Pasteur Fluzone® [15 mcg × 3 strains]) intramuscularly (IM). A self-administered memory aid recorded temperature and systemic and local adverse events (AEs) for 8 days, and safety was evaluated and serum obtained to measure HAI activity on days 7, 21 and 180 days following vaccination.ResultsA greater proportion of RA subjects who received HD seroconverted at day 21 compared to SD, although this was not statistically significant. GMT antibody responses in RA subjects who received HD compared to SD were greater for all strains on day 21, and this was significant for H1N1. Seroconversion rates and GMT values were not different between RA subjects and control subjects. There were no safety concerns for HD or SD in RA subjects, and RA-related symptoms did not differ between SD and HD recipients by a RA-symptom questionnaire (RAPID 3).ConclusionsTNF-inhibitor therapy in people with RA did not appear to influence the immunogenicity of either SD or HD. Influenza seroconversion and GMT values were higher among RA subjects receiving HD compared to SD; however, differences were small and a larger study is needed to validate these findings. Given the apparent risk of increased influenza-related morbidity and mortality among immune compromised subjects, the higher GMT values generated by HD may be beneficial.     

The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.     

Identification of B cell epitopes of Per a 5 allergen using bioinformatic approach

BackgroundImmune epitopes of allergens are pivotal for development of novel diagnostic and therapeutic modalities. Present study aims to identify antigenic determinants of Per a 5, a clinically relevant cross reactive cockroach allergen.MethodsThe three dimensional structure of Per a 5 was modelled using Modeller 9v11 software. A combination of sequence and structure based computational tools were employed for predicting B cell epitopes. Epitopes were synthesized and immunoreactivity was assessed by ELISA using cockroach hypersensitive patient’s sera. Cross-reactivity potential of predicted epitopes was assessed with SDAP and ConSurf and validated by IgE ELISA with fungal and mite hypersensitive patient’s sera.ResultsPer a 5 structure exhibited good quality factor in ERRAT and high stereochemical stability. In silico analysis revealed six B cell epitopes (BC-P1 to P6). BC-P3 demonstrated significant IgE binding followed by BC-P2 and BC-P1 with cockroach hypersensitive patient’s sera. Per a 5 epitopes demonstrate considerable similarity with broad spectrum of allergens from fungal, mites, helminths, fruits and nuts. Analysis of PD values indicate BC-P4 to be well conserved among dust mite and helminth GSTs (8.89, 10.63 and 10.69 with D. pteronyssinus, W. bancrofti and F. hepatica respectively). ConSurf analysis of Per a 5 revealed specific enrichment of evolutionarily similar amino acid residues in BC-P2 (with fungal and mite GSTs) and BC-P4 (with mite and helminth GSTs). Further, IgE binding analysis of epitopes demonstrate BC-P2, BC-P3 and BC-P5 as high IgE binders in fungal hypersensitive sera while BC-P1, BC-P2, BC-P4 and BC-P5 demonstrated significant IgE binding with mite hypersensitive sera.ConclusionsAmong the predicted epitopes, BC-P3 demonstrates maximal IgE binding ability. Computational analysis suggests strong evolutionary conservation and cross reactive potential of BC-P4 with allergens in dust mite and helminths. ELISA highlights predictive potential of analysing evolutionarily conserved residues for uncovering potentially cross reactive antigenic determinants.General significanceImmune epitopes of Per a 5 were identified for aiding molecular diagnosis and potential cross reactivity.     

Microsatellite instability profiling in Egyptian bladder cancer patients: A pilot study

Microsatellite alterations have been implicated in the pathogenesis of many cancers; however, they are still not well addressed in the bladder cancer (BC) of Egyptian population. We assessed microsatellite instability (MSI) profile and loss of heterozygosity (LOH) using 13 microsatellite markers in tumor tissue samples and urine sediments obtained from 30 Egyptian patients with BC. The concordance between MSI in tumor tissue and urine samples was determined, and correlated to relevant clinicopathologic features. We found that MSI was more frequent than LOH (100% and 46.7%, respectively). D16S310, MBP, and IFN-α showed the highest MSI frequency in urine samples (70%, 70%, and 66.67%, respectively), while MBP, ACTBP2, and D9S171 (66.67%, 63.33%, and 60%, respectively) were the most frequently detected in tumor tissues. All assessed MSI markers correlated significantly with pathologic subtype (being more frequent in TCC) and with hematuria. The concordance between tissue and urine samples was statistically significant for D16S476, D9S171, FGA, and ACTBP2 (P = 0.04, 0.015, 0.02, and 0.007, respectively). When we combined D16S476 and D9S171, the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of BC were 80.0%, 75.0%, 82.8%, and 71.4%, respectively. Accordingly, we concluded that MSI in urine sediments could be a potential tool for the diagnosis of BC.     

Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

1. Download : Download high-res image (228KB)
2. Download : Download full-size image

     

Genetic diversity of HLA system in a population from Guerrero,Mexico

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 144 Mexicans from the state of Guerrero to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes in the state of Guerrero include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Guerrero are Native American (61.36 ± 2.69% by ML; 54.17% of Native American haplotypes) and European (35.01 ± 4.59% by ML; 32.29% of European haplotypes), and a relatively low African genetic component (3.63 ± 2.38% by ML; 5.90% of African haplotypes).