Respiratory syncytial virus type A (RSV-A) is a highly contagious pathogen primarily transmitted through respiratory droplets, direct contact with infected individuals, or contaminated surfaces. The virus enters the host through the mucous membranes of the eyes, nose, or mouth, and subsequently replicates in epithelial cells of the upper and lower respiratory tracts. RSV-A is a leading cause of severe respiratory infections, particularly in infants, the elderly, and immunocompromised individuals. Its pathogenesis involves viral attachment to host cells via the G glycoprotein, which binds to cellular receptors such as heparan sulfate and CX3CR1, facilitating F glycoprotein-mediated fusion and entry. This triggers inflammation, airway hyperresponsiveness, and mucus hypersecretion, often leading to bronchiolitis or pneumonia.
RSV-A belongs to the Pneumoviridae family and has a nonsegmented, negative-sense, single-stranded RNA genome of approximately 15.2 kilobase pairs. The viral envelope is covered with three transmembrane glycoproteins: the attachment glycoprotein (G), the fusion glycoprotein (F), and the small hydrophobic protein (SH), which regulate host cell entry and immune responses. The F glycoprotein is highly conserved among RSV strains and, due to its role in membrane fusion, is a key target for vaccine development. Within the virus, the genome is tightly associated with the nucleoprotein (N) to form a ribonucleoprotein complex, while the phosphoprotein and large polymerase (L) promote RNA transcription and replication. The genome encodes 11 proteins, including the matrix (M) protein, which is involved in viral assembly, and the M2-1 and M2-2 proteins, which are involved in transcriptional regulation.
Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization and mortality in infants under six months of age worldwide. Therefore, preventing RSV infection in all infants is a major unmet medical need. Here, researchers report the isolation of a potent, broadly neutralizing RSV monoclonal antibody derived from human memory B cells. The antibody, RB1, is equally potent against RSV A and B subtypes, potently neutralizes multiple clinical isolates in vitro, and is protective in vivo. It binds to a highly conserved epitope in antigenic site IV of the RSV fusion glycoprotein. RB1 is the parent antibody of MK-1654, currently in clinical development for the prevention of RSV infection in infants.
Here, the researchers evaluated the prophylactic antiviral activity of RB1 in the cotton rat (Sigmodon hispidus) model of RSV infection. A weight-based dose of RB1 was administered via a single intramuscular injection of the antibody on day 0. Serum was collected the next day to determine the circulating concentration of RB1. After blood sampling, each animal was immediately sedated and challenged with 1 × 105 pfu of RSV strain A2 or strain B 18537 via intranasal injection. Four days after viral challenge, animals were euthanized and nasal and lung tissues were collected to evaluate antibody efficacy by measuring RSV infection titers in these tissues. The lower respiratory tract (lung) EC50 values of the RB1 antibody against RSV A and RSV B strains were 1.1 μg/mL and 1.9 μg/mL, respectively (Figure 1a, c). After RB1 administration, the EC50 values of RSV A and RSV B strains in the upper respiratory tract (nasal cavity) were 9.9 μg/mL and 8.5 μg/mL, respectively (Figure 1b, d). These in vivo data indicate that RB1 exhibits potent and dose-dependent antiviral activity in the lungs and nasal cavity after infection with RSV subtypes A and B, and the potency of the two subtypes is roughly the same.
Figure 1. Efficacy of RB1 in the upper and lower respiratory tracts of cotton rats. (Tang A, et al., 2019)
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Significantly streamlining our workflow
Creative Biogene's Wild-Type Respiratory Syncytial Virus Type A (RSV-A) is exceptional. We used it for antiviral screening, and the viral titer was spot-on. The preparation arrived intact and ready to use, significantly streamlining our workflow.
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