Delta and Omicron variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are remarkably contagious, and have been recognized as variants of concern (VOC). The acquisition of spontaneous substitutions or insertion-deletion mutations (indels) in the spike protein-encoding gene substantially increases the binding affinity of the receptor binding domain (RBD)-hACE2 complex and upsurges the transmission of both variants. In this study, we analyzed thousands of genome sequences from 30 distinct SARS-CoV-2 variants, focusing on the unique nucleic acid signatures in the spike gene specific to the Delta and Omicron variants.
View Article and Find Full Text PDFSignaling interactions are important during skeletal muscle regeneration, where muscle cells in distinct states (quiescent, reactivated, proliferating and differentiated) must coordinate their response to injury. Here, we probed the role of secreted small extracellular vesicles (sEV/exosomes) using a culture model of physiologically relevant cell states seen in muscle regeneration. Unexpectedly, G myoblasts exhibited enhanced secretion of sEV (∼150 nm) displaying exosome markers (Alix, TSG101, flotillin-1, and CD9), and increased expression of Kibra, a regulator of exosome biogenesis.
View Article and Find Full Text PDFBackground: Globally, recent estimates have shown there have been 3·6 million stillbirths and neonatal deaths in 2022, with nearly 60% occurring in low-income and middle-income countries. The Small Vulnerable Newborn Consortium has proposed a framework combining preterm birth (<37 weeks of gestation), small for gestational age (SGA) by INTERGROWTH-21st standard, and low birthweight (<2500 g) under the category small vulnerable newborns (SVN). Reliable data on SVN from sub-Saharan Africa, central Asia, and south Asia are sparse.
View Article and Find Full Text PDFBackground: Accurate assessment of gestational age (GA) and identification of preterm birth (PTB) at delivery is essential to guide appropriate post-natal clinical care. Undoubtedly, dating ultrasound sonography (USG) is the gold standard to ascertain GA, but is not accessible to the majority of pregnant women in low- and middle-income countries (LMICs), particularly in rural areas and small secondary care hospitals. Conventional methods of post-natal GA assessment are not reliable at delivery and are further compounded by a lack of trained personnel to conduct them.
View Article and Find Full Text PDFMeasuring SARS-CoV-2-specific T cell responses is crucial to understanding an individual's immunity to COVID-19. However, high inter- and intra-assay variability make it difficult to define T cells as a correlate of protection against COVID-19. To address this, we performed systematic review and meta-analysis of 495 datasets from 94 original articles evaluating SARS-CoV-2-specific T cell responses using three assays - Activation Induced Marker (AIM), Intracellular Cytokine Staining (ICS), and Enzyme-Linked Immunospot (ELISPOT), and defined each assay's quantitative range.
View Article and Find Full Text PDFIntroduction: Preeclampsia (PE) arises due to defective spiral artery remodelling which may be due to deficient migration of trophoblast cells. Migration of human endothelial cells has been shown to be promoted via Hydrogen sulphide(HS)/Rho GTPase Rac1 axis. This novel role of HS and its downstream processes have not yet been studied in the development and function of the placental trophoblast cells.
View Article and Find Full Text PDFBackground: Despite having the highest number of preterm births globally, no genomic study on preterm birth was previously published from India or other South-Asian countries.
Methods: We conducted a genome-wide association (GWA) study of spontaneous preterm birth (sPTB) on 6211 women from India. We used a novel resampling procedure to identify the associated single nucleotide polymorphisms (SNPs) followed by haplotype association analysis and imputation.
We performed an epigenome-wide longitudinal DNA methylation study on an Indian cohort of pregnant women, GARBH-Ini, at three time points during pregnancy and at delivery. Our aim was to identify temporal DNA methylation changes in maternal peripheral blood during the period of gestation and assess their impact on biological pathways critical for term delivery. Significantly differentially methylated CpGs were identified by linear mixed model analysis (Bonferroni p < 0.
View Article and Find Full Text PDFUnderstanding the quality of immune repertoire triggered during natural infection can provide vital clues that form the basis for development of a humoral immune response in some individuals capable of broadly neutralizing pan-SARS-CoV-2 variants. In the present study, we report variations in neutralization potential against Omicron variants of two novel neutralizing monoclonal antibodies (MAbs), THSC20.HVTR11 and THSC20.
View Article and Find Full Text PDFExosomes are small extracellular vesicles secreted by cells and have a major role in cell-to-cell signaling. As dengue infection progresses from a mild to a severe form of infection, the exosome's microRNA (miRNA) composition might change, which may contribute to pathogenesis. In this study, a comprehensive analysis of serum exosomal miRNAs was performed and their involvement in dengue virus-induced disease progression in an Indian cohort was assessed.
View Article and Find Full Text PDFPreterm birth (PTB) is one of the most important problems that pose dilemmas for both the obstetrician and neonatologist, placing a heavy burden psychologically and financially on the families involved, and triggering high socio-economic costs to the public healthcare. The rate of PTB in Asian countries has been ranked at top globally. To reduce the PTB rate, to promote the prevention and intervention for PTB, and to better understand the pathophysiology underlying PTB, the Preterm Birth International Collaborative Australia branch (PREBIC-AA) was launched in 2017.
View Article and Find Full Text PDFBBV152 is a whole-virion inactivated vaccine based on the Asp614Gly variant. BBV152 is the first alum-imidazoquinolin-adjuvanted vaccine authorized for use in large populations. Here we characterized the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months post vaccination.
View Article and Find Full Text PDFStringent balance of the immune system is a key regulatory factor in defining successful implantation, fetal development, and timely parturition. Interference in these primary regulatory mechanisms, either at adolescence or prenatal state led to adverse pregnancy outcomes. Fertility restoration with the help of injectable gonadotrophins/progesterone, ovulation-inducing drugs, immunomodulatory drugs (corticosteroids), and reproductive surgeries provides inadequate responses, which manifest its own side effects.
View Article and Find Full Text PDFAlthough efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of five neutralizing mAbs from an Indian convalescent donor, out of which two (THSC20.
View Article and Find Full Text PDFEBioMedicine
April 2022
Background: Rapid spread of the omicron SARS-CoV-2 variant despite extensive vaccination suggests immune escape. The neutralising ability of different vaccines alone or with natural SARS-CoV-2 infection against omicron is not well-known.
Methods: In this cross-sectional study, we tested the ability of vaccine and natural infection induced antibodies to neutralise omicron variant in a live virus neutralisation assay in four groups of individuals: (i) ChAdOx1 nCoV-19 vaccination, (ii) ChAdOx1 nCoV-19 vaccination plus prior SARS-CoV-2 infection, (iii) vaccination with inactivated virus vaccine (BBV152), and (iv) BBV152 vaccination plus prior SARS-CoV-2 infection.
Lancet Infect Dis
April 2022
Background: SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.
View Article and Find Full Text PDFNon-typhoidal (NTS) infections result in self limiting gastroenteritis except in rare cases wherein manifestations of chronic infections can occur. Strategies employed by to thrive in hostile environments of host during chronic infections are complex and multifaceted. In chronic state, a coordinated action of bacterial effectors allows reprogramming of macrophages to M2 subtype and thereby creating a permissible replicative niche.
View Article and Find Full Text PDFProblem: Small for gestational age (SGA) neonates are vulnerable to various long and short-term adverse health consequences. The expression of HLA-G in the placenta is crucial for establishment and maintenance of pregnancy. Its aberrant expression could lead to perturbed immunological interactions in the placenta which could be associated with SGA births.
View Article and Find Full Text PDFThe spike protein of the SARS-CoV-2 virus is the foremost target for the designing of vaccines and therapeutic antibodies and also acts as a crucial antigen in the assessment of COVID-19 immune responses. The enveloped viruses; such as SARS-CoV-2, Human Immunodeficiency Virus-1 (HIV-1) and influenza, often hijack host-cell glycosylation pathways and influence pathobiology and immune selection. These glycan motifs can lead to either immune evasion or viral neutralization by the production of cross-reactive antibodies that can lead to antibody-dependent enhancement (ADE) of infection.
View Article and Find Full Text PDFFront Cell Infect Microbiol
July 2021
Background: The incidence of preterm birth (PTB) in India is around 13%. Specific bacterial communities or individual taxon living in the vaginal milieu of pregnant women is a potential risk factor for PTB and may play an important role in its pathophysiology. Besides, bacterial taxa associated with PTB vary across populations.
View Article and Find Full Text PDFClinical and epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available, but there are few data regarding longitudinal serology in large cohorts, particularly those from low-income and middle-income countries. We established an ongoing prospective cohort of 3,840 SARS-CoV-2-positive individuals according to RT-PCR in the Delhi-National Capital Region of India to document clinical and immunological characteristics during illness and convalescence. The immunoglobulin G (IgG) responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0 to 7 days, 10 to 28 days, and 6 to 10 weeks after infection.
View Article and Find Full Text PDFFront Microbiol
January 2021
SARS-CoV-2 antibody detection assays are crucial for gathering seroepidemiological information and monitoring the sustainability of antibody response against the virus. The SARS-CoV-2 Spike protein's receptor-binding domain (RBD) is a very specific target for anti-SARS-CoV-2 antibodies detection. Moreover, many neutralizing antibodies are mapped to this domain, linking antibody response to RBD with neutralizing potential.
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