ArticleNature communications2024
Efficacious human metapneumovirus vaccine based on AI-guided engineering of a closed prefusion trimer.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed.
- Clinical Features and Predictors of Severity in Children Hospitalized With Human Metapneumovirus: A Multicenter Italian Study.The Pediatric infectious disease journal · 2026Observational
- Stabilization of prefusion hMPV F improves manufacturability and protective immunity across hMPV lineages.Virologica Sinica · 2026Article
- Disease Spectrum of Human Metapneumovirus Infections in Infants and Young Children: Data From a Prospective Multicenter Study in Germany.The Pediatric infectious disease journal · 2026Article
- Human Metapneumovirus (HMPV): Advances in Diagnosis, Molecular Epidemiology, and Clinical Impact of an Underrecognized Respiratory Virus.Diagnostics (Basel, Switzerland) · 2026Review
- Structural vaccinology expedites rational design of next-generation vaccines for influenza and respiratory syncytial virus.Virologica Sinica · 2026Review
- Mechanistic insights and emerging applications of human metapneumovirus (HMPV) treatment: From molecular design to translational immunity.Folia microbiologica · 2026Review
- AI-guided prefusion stabilization of the human coronavirus OC43 spike protein enables universal embecovirus antigen design.PLoS pathogens · 2026Article
- Development of a potent monoclonal antibody for treatment of human metapneumovirus infections.Nature communications · 2026Article
- HERMES: Holographic Equivariant neuRal network model for Mutational Effect and Stability prediction.bioRxiv : the preprint server for biology · 2026Article
- Article
- Rational design and in silico characterization of a multiepitope mRNA vaccine candidate against human metapneumovirus (hMPV) using reverse vaccinology and immunoinformatics approaches.Scientific reports · 2025Article
- Human Metapneumovirus and Respiratory Syncytial Virus in Children: A Comparative Analysis.Pediatrics · 2025Article
- Human Metapneumovirus: A Narrative Review on Emerging Strategies for Prevention and Treatment.Viruses · 2025Review
- A second-generation molecular clamp stabilised bivalent candidate vaccine for protection against diseases caused by respiratory syncytial virus and human metapneumovirus.PLoS pathogens · 2025Article
- Immunological insights into the re-emergence of human metapneumovirus.Current opinion in immunology · 2025Review
- The surge of human metapneumovirus (hMPV) cases in China and global implications.New microbes and new infections · 2025Article
- Article
- Article
- A foldon-free prefusion F trimer vaccine for respiratory syncytial virus to reduce off-target immune responses.Nature microbiology · 2024Article
- Engineering a cleaved, prefusion-stabilized influenza B virus hemagglutinin by identification and locking of all six pH switches.PNAS nexus · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces. To identify these substitutions, we developed an AI convolutional classifier that successfully predicts complex polar interactions often overlooked by physics-based methods and visual inspection. The combination of additional processing, stabilization of interface regions and stabilization of the membrane-proximal stem, resulted in a Pre-F protein vaccine candidate without the need for a heterologous trimerization domain that exhibited high expression yields and thermostability. Cryo-EM analysis shows the complete ectodomain structure, including the stem, and a specific interaction of the newly identified cleaved C-terminus with the adjacent protomer. Importantly, the protein induces high and cross-neutralizing antibody responses resulting in near complete protection against hMPV challenge in cotton rats, making the highly stable, double-cleaved hMPV Pre-F trimer an attractive vaccine candidate.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.