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The intricate regulation of gene expression is fundamental to the biological complexity of higher organisms, and is primarily governed by transcriptional and post-transcriptional mechanisms. The 3'-untranslated region (3'UTR) of mRNA is rich in cis-regulatory elements like G-quadruplexes (G4s), and plays a crucial role in post-transcriptional regulation. G4s have emerged as significant gene regulators, impacting mRNA stability, translation, and localization. In this study, we investigate the role of a robust parallel G4 structure situated within the 3'UTR of CCN1 mRNA in post-transcriptional regulation. This G4 structure is proximal to the stop codon of human CCN1, and evolutionarily conserved. We elucidated its interaction with the insulin-like growth factor 2 binding protein 1 (IGF2BP1), a noncanonical RNA N6-methyladenosine (m6A) modification reader, revealing a novel interplay between RNA modifications and G-quadruplex structures. Knockdown experiments and mutagenesis studies demonstrate that IGF2BP1 binds specifically to the G4 structure, modulating CCN1 mRNA stability. Additionally, we unveil the role of IGF2BP1's RNA recognition motifs in G4 recognition, highlighting this enthalpically driven interaction. Our findings offer fresh perspectives on the complex mechanisms of post-transcriptional gene regulation mediated by G4 RNA secondary structures.

Background Objectives: The Omicron sub-lineages are known to have higher infectivity, immune escape and lower virulence. During December 2022 - January 2023 and March - April 2023, India witnessed increased SARS-CoV-2 infections, mostly due to newer Omicron sub-lineages. With this unprecedented rise in cases, we assessed the neutralization potential of individuals vaccinated with ChAdOx1 nCoV (Covishield) and BBV152 (Covaxin) against emerging Omicron sub-lineages., Methods: Neutralizing antibody responses were measured in the sera collected from individuals six months post-two doses (n=88) of Covishield (n=44) or Covaxin (n=44) and post-three doses (n=102) of Covishield (n=46) or Covaxin (n=56) booster dose against prototype B.1 strain, lineages of Omicron; XBB.1, BQ.1, BA.5.2 and BF.7., Results: The sera of individuals collected six months after the two-dose and the three-dose demonstrated neutralizing activity against all variants. The neutralizing antibody (NAbs) level was highest against the prototype B.1 strain, followed by BA5.2 (5-6 fold lower), BF.7 (11-12 fold lower), BQ.1 (12 fold lower) and XBB.1 (18-22 fold lower)., Interpretation Conclusions: Persistence of NAb responses was comparable in individuals with two- and three-dose groups post six months of vaccination. Among the Omicron sub-variants, XBB.1 showed marked neutralization escape, thus pointing towards an eventual immune escape, which may cause more infections. Further, the correlation of study data with complete clinical profile of the participants along with observations for cell-mediated immunity may provide a clear picture for the sustained protection due to three-dose vaccination as well as hybrid immunity against the newer variants., (Copyright © 2024 Copyright: © 2024 Indian Journal of Medical Research.)

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immunization is expected to confer protection against infection and severe disease for vaccines while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies of an observational cohort of healthcare workers, we show that during a Severe Acute Respiratory Syndrome -Coronavirus 2 Delta-variant outbreak in Delhi, 25.3% (95% Confidence Interval 16.9-35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare workers were infected within less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, Inter Quartile Range 374) and without (342 U/ml, Inter Quartile Range 497), as was the induction of neutralization activity to wildtype. This was not vaccine failure since vaccine effectiveness estimate based on infection rates in an unvaccinated cohort were about 70% and most infections were asymptomatic. We find that while ChAdOx1-nCoV19 vaccination remains effective in preventing severe infections, it is unlikely to be completely able to block transmission and provide herd immunity., (© 2022. The Author(s).)

Delhi, the national capital of India, experienced multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks in 2020 and reached population seropositivity of >50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant, B.1.617.2 (Delta), replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates: 1.5-fold greater transmissibility and 20% reduction in sensitivity). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline. The likely high transmissibility and partial evasion of immunity by the Delta variant contributed to an overwhelming surge in Delhi.

To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India) conducted a serosurvey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS-CoV2 anti-nucleocapsid (anti-NC) antibodies, 95% of which had surrogate neutralization activity. Three-fourth of these recalled no symptoms. Repeat serology tests at 3 (n = 607) and 6 (n = 175) months showed stable anti-NC antibodies but declining neutralization activity. Local seropositivity was higher in densely populated cities and was inversely correlated with a 30-day change in regional test positivity rates (TPRs). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of seropositivity were high-exposure work (odds ratio, 95% confidence interval, p value: 2.23, 1.92-2.59, <0.0001), use of public transport (1.79, 1.43-2.24, <0.0001), not smoking (1.52, 1.16-1.99, 0.0257), non-vegetarian diet (1.67, 1.41-1.99, <0.0001), and B blood group (1.36, 1.15-1.61, 0.001)., Competing Interests: SN, VS, RU, NB, RK, AB, SP, SP, RK, BR, KT, MA, GC, AL, SK, SM, MM, MS, SK, AS, BT, MV, GV, SV, AA, DG, PH, MP, GS, RV, AP, VA, AM, RS, AR, SA, PK, SV, HS, AK, RJ, AT, DP, AS, JK, VK, AM, IG, GR, PS, RC, GC, PK, RY, SS, DS, SS, PB, SA, VS, SV, DS, SS, SV, ST, FF, AS, AS, BS, MS, YP, VH, VP, DS, NT, PC, SM, DG, JS, SR, BK, KK, SG, PJ, RC, VJ, NK, DG, GT, US, PS, SC, RK, PG, AT, DS, RR, AD, MK, DS, MD, SD, RJ, AP, SM, AK, VW, RY, AK, MB, AC, SK, KK, SP, JK, NS, TP, PM, WR, PB, DO, RS, EB, RS, AN, PV, AP, AV, KC, SD, YM, VA, SD, AA, DD, SS No competing interests declared, (© 2021, Naushin et al.)