Biology subjects

Karim, M. M.

Publications and source records attributed to Karim, M. M..

3 recordsLinked to original sources

bioRxiv2020

Association of poor virus specific immunoglobulin G antibodyresponses with higher viral load is seen in Bangladeshi pregnantwomen having acute Hepatitis E Genotype 1 infection

Although Hepatitis E viral illness is usually self-limiting, higher rates of morbidity and mortality are frequently observed during pregnancy in South Asian countries including Bangladesh. Of the four common variants, hepatitis E virus genotype 1 is mainly prevalent in South Asian countries. Pregnant women usually suffer from a state of immunosuppression. It is yet to be known whether virus specific immunoglobulin G (IgG) immune responses have any association with the vulnerability of pregnant women to acute hepatitis with E virus. The study aimed to compare the viral load and IgG responses of hepatitis E-infected pregnant women with that of non-pregnant women with same infection. Real Time -quantitative reverse transcription Polymerase Chain Reaction and Sanger sequencing were performed to determine the viral load and genotype, respectively, whereas Enzyme Linked Immunosorbent Assay method was used to determine hepatitis E virus specific serum IgG antibody index along with IgG avidity index. Although significant negative correlations were observed between log viral copy number and log IgG antibody index in the late acute phases of jaundice for both pregnant (r= -0.7971, p=0.0002) and non-pregnant women (r= -0.9117, p=0.0002), serum log viral copy number of pregnant women was significantly higher than that of the non-pregnant counterpart (p=0.0196) in the late acute stage of jaundice. In addition, log hepatitis E virus IgG antibody index of pregnant women was significantly lower than the non-pregnant women in the late phase of jaundice induced by hepatitis E virus (p=0.0303). Moreover, pregnant women with acute hepatitis E had higher cross-reactive IgG than in the non-pregnant women (p=0.0017). All the patients got infected with hepatitis E virus were in Genotype 1 variety. The study demonstrates that virus-specific poor IgG responses might be responsible for vulnerability of pregnant women to acute hepatitis with hepatitis E virus. Author SummaryAcute hepatitis caused by hepatitis E virus (HEV) Genotype 1 is a public health problem in Asian countries and especially it poses a potential health threat to pregnant women causing 19% to 25% mortality, particularly in South Asian countries including Bangladesh. The study aimed to explore whether HEV IgG immune responses were compromised during pregnancy, which might contribute to higher viral load and disease severity. Accordingly, pregnant and non-pregnant women with acute hepatitis (clinically presented with nausea, loss of appetite and /or jaundice) were enrolled from different tertiary care hospitals in Dhaka city. All these patients were screened and hepatitis E were differentiated from other hepatitis (caused by A, B, C) using Enzyme Linked Immunosorbent Assay (ELISA) methods. HEV IgG antibody/avidity indices and viral loads were measured using ELISA and real time quantitative polymerase chain reaction (RT-qPCR), respectively. The study showed that pregnant women with acute hepatitis E had lower IgG indices with higher viral load than their non-pregnant counterpart. Overall, the study revealed that virus-specific poor IgG responses might render pregnant women vulnerable to acute hepatitis E of varying degree of severity which might be associated with higher viral load.

immunology↗

bioRxiv2019

Structural Basis and Designing of Peptide Vaccine using PE-PGRS Family Protein of Mycobacterium ulcerans - An Integrated Vaccinomics Approach

Buruli ulcer is an emerging-necrotizing skin infection, responsible for permanent deformity if untreated, caused by the pathogen Mycobacterium ulcerans (M. ulcerans). Despite this debilitating condition, no specific disease-modifying therapeutics or vaccination is available. Therefore, we aimed to design an effective multi-epitope vaccine against M. ulcerans through an integrated vaccinomics approach. Briefly, the highest antigenic PE-PGRS protein was selected from which the promiscuous T- and B-cell epitopes were predicted. After rigorous assessment, 15 promising CTL, HTL and LBL epitopes were selected. The identified T-cell epitopes showed marked interactions towards the HLA binding alleles and provided 99.8% world population coverage. Consequently, a vaccine chimera was designed by connecting these epitopes with suitable linkers and adjuvant (LprG). The vaccine construct was antigenic and immunogenic as well as non-allergenic; hence, subjected to homology modelling. The molecular docking and dynamic simulation revealed strong and stable binding affinity between the vaccine and TLR2 receptor. The binding energy ({Delta}G) and dissociation constant (Kd) were -15.3 kcal/mol and 5.9x10-12 M, respectively. Further, disulfide engineering was applied to improve vaccine stability and higher expression in Escherichia coli K12 system was ensured by codon optimization and cloning in silico. The computer-simulated immune responses were characterized by higher levels of IgM and IgG antibodies, helper T-cells with increased IFN-{gamma} production, and macrophage activity crucial for immunity against M. ulcerans. Therefore, our data suggest that, if the designed vaccine is validated experimentally, it will prevent Buruli ulcer by generating robust immune response against M. ulcerans.

bioinformatics↗

bioRxiv2019

Immunoinformatic and dynamic simulation-based designing of a multi-epitope vaccine against emerging pathogen Elizabethkingia anophelis

Elizabethkingia anophelis is an emerging human pathogen causing neonatal meningitis, catheter-associated infections and nosocomial outbreaks with high mortality rates. Besides, they are resistant to most antibiotics used in empirical therapy. In this study, therefore, we used immunoinformatic approaches to design an epitope-based vaccine against E. anophelis as an alternative preventive measure. Initially, T-cell (CTL and HTL) and B-cell (LBL) epitopes were predicted from the highest antigenic protein. The CTL and HTL epitopes together had a population coverage of 99.97% around the world. Eventually, 6 CTL, 7 HTL, and 2 LBL epitopes were selected and used to construct a multiepitope vaccine. The vaccine protein was found to be highly immunogenic, non-allergenic, and non-toxic. Codon adaptation and in silico cloning were performed to ensure better expression within E. coli K12 host system. The stability of the vaccine structure was also improved by disulphide bridging. In addition, molecular docking and dynamic simulation revealed good and stable binding affinity between the vaccine and receptor. The immune simulation showed higher levels of T-cell and B-cell activities which was in coherence with actual immune response. Repeated exposure simulation resulted in higher clonal selection and faster antigen clearance. Nevertheless, experimental validation is required to ensure the immunogenic potency and safety of this vaccine to control E. anophelis infection in the future.

bioinformatics↗