A5094125443- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- Parvovirus B19 Infection Studies
- vaccines and immunoinformatics approaches
- Pneumonia and Respiratory Infections
- SARS-CoV-2 and COVID-19 Research
- Diabetes and associated disorders
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Virology and Viral Diseases
- Influenza Virus Research Studies
Janssen (Netherlands)
2024
The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and preferred immunogen an efficacious vaccine against hMPV respiratory infections. Here we show that additional cleavage event in F allows closure correct folding trimer. We therefore engineered to undergo double cleavage, which enabled screening Pre-F stabilizing substitutions at natively folded protomer interfaces. To identify these...
Human respiratory syncytial virus (RSV) poses a significant human health threat, particularly to infants and the elderly. While efficacious vaccines based on F protein have recently received market authorization, uncertainties remain regarding future need for vaccine updates counteract potential viral drift. The attachment G has long been ignored as target due perceived non-essentiality ineffective neutralization immortalized cells. Here, we show strong G-based in fully differentiated airway...
The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. RV3 fusion (F) protein is inherently metastable will likely require prefusion (preF) stabilization vaccine effectiveness. Here we used structure-based design to...
Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and older people. Current RSV subunit vaccines are based on fusion protein that stabilized the prefusion conformation linked to heterologous foldon trimerization domain obtain F (preF) trimer. Here we show current induce undesirable anti-foldon antibodies non-human primates, mice humans. To overcome this, designed foldon-free preF trimer by elucidating structural basis trimerization-induced...
Abstract Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells facilitated by the attachment glycoprotein and fusion (F). Because its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures bound to prefusion conformation reveal three distinct, previously...
Abstract Vaccine components based on viral fusion proteins require high stability of the native prefusion conformation for optimal potency and manufacturability. In case influenza B virus hemagglutinin (HA), stem's relies efficient cleavage. this study, we identified six pH-sensitive regions distributed across entire ectodomain where protonated histidines assume either a repulsive or an attractive role. Substitutions in these areas enhanced protein's expression, quality, its trimeric state....