ArticleProceedings of the National Academy of Sciences of the United States of America2018
Structure-based design of a quadrivalent fusion glycoprotein vaccine for human parainfluenza virus types 1-4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 102 citations in OpenAlex.
- Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: a randomised, double-blind, placebo-controlled, phase 1 trial.The Lancet. Infectious diseases · 2021Trial
- A cavity-reduced prefusion RSV F bivalent vaccine elicits durable and protective immunity.EMBO molecular medicine · 2026Article
- Pan-neutralization of parainfluenza viruses by a hemagglutinin-neuraminidase antibody.bioRxiv : the preprint server for biology · 2026Article
- Molecular basis for protection and cross-protection by human antibodies targeting the parainfluenza virus hemagglutinin-neuraminidase protein.Journal of virology · 2026Article
- Human parainfluenza virus 3 fusion protein cleavage: a key determinant of infection and spread.Journal of virology · 2026Article
- Prefusion-stabilized Hantaan virus glycoprotein nucleic acid vaccine elicits potent neutralizing antibody responses via germinal center activation.Nature communications · 2026Article
- Mechanistic insights and emerging applications of human metapneumovirus (HMPV) treatment: From molecular design to translational immunity.Folia microbiologica · 2026Review
- Contrastive learning enables epitope overlap predictions for targeted antibody discovery.Patterns (New York, N.Y.) · 2026Article
- Structure and immunogenicity of an engineered soluble prefusion-stabilized EBV gB antigen.Nature communications · 2026Article
- Landscape of Prophylactic Strategies Against Human Parainfluenza Virus Type 3.Reviews in medical virology · 2025Review
- Broad-spectrum vaccines against various and evolving viruses: from antigen design to nanoparticle delivery.Journal of virology · 2025Review
- A Computationally Optimised Structural Integrity Sequence Enhances Vaccine Stability, Yield and Safety Profile.Research square · 2025Article
- Potent Cross-neutralizing Antibodies Reveal Vulnerabilities of Henipavirus Fusion Glycoprotein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Design, Structure, and Immunogenicity of a Soluble Prefusion-stabilized EBV gB Antigen.bioRxiv : the preprint server for biology · 2025Article
- Peptides targeting RAB11A-FIP2 complex inhibit HPIV3, RSV, and IAV replication as broad-spectrum antivirals.Cell & bioscience · 2025Article
- Molecular Evolution of theMicroorganisms · 2025Article
- The structural basis of protective and nonprotective human monoclonal antibodies targeting the parainfluenza virus type 3 hemagglutinin-neuraminidase.Nature communications · 2024Article
- Structure-based design of glycoprotein subunit vaccines for mumps.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Discovery and characterization of a pan-betacoronavirus S2-binding antibody.Structure (London, England : 1993) · 2024Article
- How a paramyxovirus fusion/entry complex adapts to escape a neutralizing antibody.Nature communications · 2024Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 5 institutions in 2 countries.
Funding
Abstract
Parainfluenza virus types 1-4 (PIV1-4) are highly infectious human pathogens, of which PIV3 is most commonly responsible for severe respiratory illness in newborns, elderly, and immunocompromised individuals. To obtain a vaccine effective against all four PIV types, we engineered mutations in each of the four PIV fusion (F) glycoproteins to stabilize their metastable prefusion states, as such stabilization had previously enabled the elicitation of high-titer neutralizing antibodies against the related respiratory syncytial virus. A cryoelectron microscopy structure of an engineered PIV3 F prefusion-stabilized trimer, bound to the prefusion-specific antibody PIA174, revealed atomic-level details for how introduced mutations improved stability as well as how a single PIA174 antibody recognized the trimeric apex of prefusion PIV3 F. Nine combinations of six newly identified disulfides and two cavity-filling mutations stabilized the prefusion PIV3 F immunogens and induced 200- to 500-fold higher neutralizing titers in mice than were elicited by PIV3 F in the postfusion conformation. For PIV1, PIV2, and PIV4, we also obtained stabilized prefusion Fs, for which prefusion versus postfusion titers were 2- to 20-fold higher. Elicited murine responses were PIV type-specific, with little cross-neutralization of other PIVs. In nonhuman primates (NHPs), quadrivalent immunization with prefusion-stabilized Fs from PIV1-4 consistently induced potent neutralizing responses against all four PIVs. For PIV3, the average elicited NHP titer from the quadrivalent immunization was more than fivefold higher than any titer observed in a cohort of over 100 human adults, highlighting the ability of a prefusion-stabilized immunogen to elicit especially potent neutralization.
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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.