Biology subjects

Talukdar, S. N.

Publications and source records attributed to Talukdar, S. N..

5 recordsLinked to original sources

bioRxiv2026

Sex differences in vaccine-induced neuraminidase cross-recognition and protection against H5N1 in mice

H5N1 vaccines have been poorly immunogenic in humans, creating a challenge for vaccine development. Seasonal influenza vaccines offer some cross-protection against H5N1, but there has been no consideration of whether protection differs between the sexes. We investigated sex differences in antibody responses following receipt of either beta-propiolactone inactivated whole virus H1N1 or H5N1 (LAIV backbone) vaccines in C57BL/6 mice. Using systems serology assays, vaccination induced strong homologous and heterologous antibody responses, with females generating greater IgG titers than males against whole virus H1N1 and H5N1, which was primarily mediated by greater IgG responses to neuraminidase (NA) than hemagglutinin (HA) protein. Cross-reactive H5N1 IgG titers were greater among H1N1-vaccinated females, and primarily mediated by greater N1-specific IgG titers. IgG2b and IgG2c were the primary antibody isotypes generated in response to these vaccines, with females having greater IgG2b titers and enhanced binding to Fc{gamma}RIV for avian and human NA than males following either homologous or heterologous vaccination. Antibody-dependent complement deposition was measured as an FcR-mediated non-neutralizing response against HA and NA and was more robust among H1N1 and H5N1 vaccinated females than their male counterparts in response to homologous HA only. Vaccinated females tended to have greater neutralizing antibody titers than males against the homologous vaccine strain, with limited cross-neutralizing antibodies detected in either sexes. Neuraminidase inhibition titers were greater in vaccinated females than males against the heterologous virus following H1N1 vaccination and against both the vaccine and heterologous viruses following H5N1 vaccination. When H1N1 and H5N1 vaccinated mice were challenged with a lethal dose of A/Texas/37/2024 H5N1, all H5N1 vaccinated mice were protected, regardless of sex. Among H1N1 vaccinated mice, while both sexes were protected against disease, H1N1 vaccinated females restricted virus to the upper respiratory tract and had lower pulmonary virus titers than males at 3 days post challenge. These findings highlight that sex differences in vaccine-induced NA-specific antibody responses are associated with differential respiratory dissemination of H5N1 and that sex should be considered in studies of vaccine-induced cross-reactive influenza immunity.

immunology↗

bioRxiv2025

Vertical Transmission of Bovine H5N1 during Pregnancy and Lactation in Mice

Avian influenza H5N1 has pandemic potential and historically has caused more severe disease in pregnant women than the general population. With increasing transmission of H5N1 detected among placental mammals, animal models are necessary for testing countermeasures, including during pregnancy. Pregnant outbred mice were infected with a contemporary strain of bovine H5N1 during the second or third trimester equivalent. Second trimester infection caused in utero transmission, with infectious virus detected in the uterus, placenta, and fetus. Birth following third trimester infection resulted in offspring with decreased size, neurodevelopmental delays, and adolescent behavioral impairments, with infectious virus detected in the neonatal milk ring and lungs, as well as mammary tissues. H5N1 viral protein colocalized with trophoblast cells in the placenta and epithelial cells in mammary tissue that spatially overlapped with lectins for 2,3-linked SA. With the pandemic potential of H5N1, our vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.

microbiology↗

bioRxiv2023

RSV infection does not induce EMT

Respiratory syncytial virus (RSV) infection does not cause severe disease in most of us despite suffering from multiple RSV infections in our lives. However, infants, young children, older adults, and immunocompromised patients are unfortunately vulnerable to RSV-associated severe diseases. A recent study suggested that RSV infection causes cell expansion, resulting in bronchial wall thickening in vitro. Whether the virus-induced changes in the lung airway resemble epithelial-mesenchymal transition (EMT) is still unknown. Here, we report that RSV does not induce EMT in three different in vitro lung models: the epithelial A549 cell line, primary normal human bronchial epithelial cells, and pseudostratified airway epithelium. We found that RSV increases the cell surface area and perimeter in the infected airway epithelium, which is distinct from the effects of a potent EMT inducer, TGF-{beta}1-driven cell elongation--indicative of cell motility. A genome-wide transcriptome analysis revealed that both RSV and TGF-{beta}1 have distinct modulation patterns of the transcriptome, which suggests that RSV-induced changes are distinct from EMT.

microbiology↗

bioRxiv2022

RSV-induced Expanded Ciliated Cells Contribute to Bronchial Wall Thickening

Viral infection, particularly respiratory syncytial virus (RSV), causes inflammation in the bronchiolar airways (bronchial wall thickening, also known as bronchiolitis), reducing airflow through the bronchioles. This bronchial wall thickening is a common pathophysiological feature in RSV infection, but it causes more fatalities in infants than in children and adults. However, the molecular mechanism of RSV-induced bronchial wall thickening remains unknown, particularly in healthy adults. RSV infection in the airway epithelium of healthy adult bronchial cells reveals RSV-infects primarily ciliated cells. RSV infection expands the cell cytoskeleton substantially without compromising epithelial membrane integrity and ciliary functions. The RSV-induced actin cytoskeleton expansion increases ununiformly epithelial height, and cytoskeletal (actin polymerization), immunological (INF-L1, TNF-, IP10/CXCL10), and viral (NS2) factors are probably responsible. Interestingly, RSV-infected cell cytoskeletons expansion resembles a noncanonical inflammatory phenotype, which contributes to bronchial wall thickening, and is termed cytoskeletal inflammation. Author SummaryRSV infects everyone. Although RSV-induced fatal pathophysiology (e.g., bronchiolitis) is more common in infants than adults, this bronchiolitis (or bronchial wall thickening) is common in the lower respiratory tract due to RSV infection in all ages. To determine the molecular mechanism of RSV-induced bronchial wall thickening, we infected in vitro adult airway epithelium with RSV. We found that RSV-infection induced a substantial actin-cytoskeleton expansion, consequently increased the height of the epithelium. We identified actin polymerization, secretion of proinflammatory cytokines and chemokines, and viral proteins contribute to the RSV-induced cytoskeletal expansion. Our results suggest that RSV-induces a novel noncanonical epithelial host response termed cytoskeletal inflammation, which may contribute to bronchial wall thickening.

microbiology↗

bioRxiv2020

Goblet Cell Hyperplasia Increases SARS-CoV-2 Infection in COPD

SARS-CoV-2 has become a major problem across the globe, with approximately 50 million cases and more than 1 million deaths and currently no approved treatment or vaccine. Chronic obstructive pulmonary disease (COPD) is one of the underlying conditions in adults of any age that place them at risk for developing severe illness associated with COVID-19. We established an airway epithelium model to study SARS-CoV-2 infection in healthy and COPD lung cells. We found that both the entry receptor ACE2 and the co-factor transmembrane protease TMPRSS2 are expressed at higher levels on nonciliated goblet cell, a novel target for SARS-CoV-2 infection. We observed that SARS-CoV-2 infected goblet cells and induced syncytium formation and cell sloughing. We also found that SARS-CoV-2 replication was increased in the COPD airway epithelium likely due to COPD associated goblet cell hyperplasia. Our results reveal goblet cells play a critical role in SARS-CoV-2 infection in the lung.

microbiology↗