Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention
Open accessAbstract
Human respiratory syncytial virus (hRSV) is the most important viral agent of pediatric respiratory infections worldwide. The only specific treatment available today is a humanized monoclonal antibody (Palivizumab) directed against the F glycoprotein, administered prophylactically to children at very high risk of severe hRSV infections. Palivizumab, as most anti-F antibodies so far described, recognizes an epitope that is shared by the two conformations in which hRSV_F can fold, the metastable prefusion form and the highly stable postfusion conformation. We now describe a unique class of antibodies specific for the prefusion form of this protein that account for most of the neutralizing activity of either a rabbit serum raised against a vaccinia virus recombinant expressing hRSV_F or a human Ig preparation (Respigam), which was used for prophylaxis before Palivizumab. These antibodies therefore offer unique possibilities for immune intervention against hRSV, and their production should be assessed in trials of hRSV vaccines.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The major target of RSV-neutralizing antibodies elicited by natural infection resides primarily on the prefusion conformation of RSV F.
“Recently, however, the major target of RSV-neutralizing antibodies elicited by natural infection was found to reside primarily on the prefusion conformation of RSV F (10).”
From Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus (2013) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Nair, H., Nokes, D. J., Gessner, B. D., Dherani, M., Madhi, S. A., Singleton, R. J., O'Brien, K. L., Roca, A., Wright, P. F., Bruce, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60206-1 · Cited by 2,773 · see citing works
Respiratory Syncytial Virus Infection in Elderly and High-Risk Adults
Falsey, A. R., Hennessey, P., Formica, M. A., Cox, C., & Walsh, E. E. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043951 · Cited by 2,239 · see citing works
KIM, H. W., CANCHOLA, J. G., BRANDT, C. D., PYLES, G., CHANOCK, R. M., JENSEN, K., & PARROTT, R. H. (1969) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a120955 · Cited by 1,981 · see citing works
Risk of Primary Infection and Reinfection With Respiratory Syncytial Virus
Glezen, W. P. (1986) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1986.02140200053026 · Cited by 1,517 · see citing works
The IMpact-RSV Study Group (1998) · Pediatrics · doi:10.1542/peds.102.3.531 · Cited by 1,201 · see citing works
Immunity to and Frequency of Reinfection with Respiratory Syncytial Virus
Hall, C. B., Walsh, E. E., Long, C., & Schnabel, K. C. (1991) · The Journal of Infectious Diseases · doi:10.1093/infdis/163.4.693 · Cited by 774 · see citing works
Groothuis, J. R., Simoes, E., Levin, M. J., Hall, C. B., Long, C. E., Rodriguez, W. J., Arrobio, J., Meissner, H. C., Fulton, D. R., Welliver, R. C., et al. (1993) · New England Journal of Medicine · doi:10.1056/nejm199311183292102 · Cited by 744 · see citing works
Delgado, M. F., Coviello, S., Monsalvo, A. C., Melendi, G. A., Hernandez, J. Z., Batalle, J. P., Diaz, L., Trento, A., Chang, H.-Y., Mitzner, W., et al. (2008) · Nature Medicine · doi:10.1038/nm.1894 · Cited by 498 · see citing works
Self-citationMcLellan, J. S., Yang, Y., Graham, B. S., & Kwong, P. D. (2011) · Journal of Virology · doi:10.1128/jvi.00555-11 · Cited by 433 · see citing works
Paramyxovirus Fusion: A Hypothesis for Changes
Lamb, R. A. (1993) · Virology · doi:10.1006/viro.1993.1561 · Cited by 420 · see citing works
Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation
Yin, H.-S., Wen, X., Paterson, R. G., Lamb, R. A., & Jardetzky, T. S. (2006) · Nature · doi:10.1038/nature04322 · Cited by 418 · see citing works
Structural characterization of the human respiratory syncytial virus fusion protein core
Zhao, X., Singh, M., Malashkevich, V. N., & Kim, P. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.260499197 · Cited by 290 · see citing works
Swanson, K. A., Settembre, E. C., Shaw, C. A., Dey, A. K., Rappuoli, R., Mandl, C. W., Dormitzer, P. R., & Carfi, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106536108 · Cited by 285 · see citing works
Structural basis of viral invasion: lessons from paramyxovirus F
Lamb, R. A., & Jardetzky, T. S. (2007) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2007.08.016 · Cited by 260 · see citing works
González-Reyes, L., Ruiz-Argüello, M. B., García‐Barreno, B., Calder, L. J., López, J. A., Albar, J. P., Skehel, J. J., Wiley, D. C., & Melero, J. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151098198 · Cited by 242 · see citing works
Self-citationStott, E. J., Taylor, G., Ball, L. A., Anderson, K., Young, K. K., King, A. M. Q., & Wertz, G. W. (1987) · Journal of Virology · doi:10.1128/jvi.61.12.3855-3861.1987 · Cited by 214 · see citing works
Immunoprophylaxis and immunotherapy of respiratory syncytial virus infection in the cotton rat
Prince, G. A., Hemming, V. G., Horswood, R. L., & Chanock, R. M. (1985) · Virus Research · doi:10.1016/0168-1702(85)90045-0 · Cited by 214 · see citing works
Connors, M., Collins, P. L., Firestone, C.-Y., & Murphy, B. R. (1991) · Journal of Virology · doi:10.1128/jvi.65.3.1634-1637.1991 · Cited by 204 · see citing works
Structural basis of respiratory syncytial virus neutralization by motavizumab
McLellan, J. S., Chen, M., Kim, A., Yang, Y., Graham, B. S., & Kwong, P. D. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1723 · Cited by 182 · see citing works
Relationship of Serum Antibody to Risk of Respiratory Syncytial Virus Infection in Elderly Adults
Falsey, A. R., & Walsh, E. E. (1998) · The Journal of Infectious Diseases · doi:10.1086/517376 · Cited by 173 · see citing works
Antigenic Structure of Human Respiratory Syncytial Virus Fusion Glycoprotein
López, J. A., Bustos, R., Örvell, C., Berois, M., Arbiza, J., García‐Barreno, B., & Melero, J. A. (1998) · Journal of Virology · doi:10.1128/jvi.72.8.6922-6928.1998 · Cited by 123 · see citing works
Self-citationCalder, L. J., González-Reyes, L., García‐Barreno, B., Wharton, S. A., Skehel, J. J., Wiley, D. C., & Melero, J. A. (2000) · Virology · doi:10.1006/viro.2000.0279 · Cited by 109 · see citing works
Self-citationConnolly, S. A., Leser, G. P., Yin, H.-S., Jardetzky, T. S., & Lamb, R. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608678103 · Cited by 95 · see citing works
Chaiwatpongsakorn, S., Epand, R. F., Collins, P. L., et al. (2011) · Journal of Virology · doi:10.1128/jvi.01813-10 · Cited by 63 · see citing works
Magro, M., Andreu, D., Gómez‐Puertas, P., et al. (2010) · Journal of Virology · doi:10.1128/jvi.00447-10 · Cited by 59 · see citing works
Self-citationGraham, B. S., Davis, T. H., Tang, Y., et al. (1993) · Pediatric Research · doi:10.1203/00006450-199308000-00013 · Cited by 50 · see citing works
Variable Resistance to Palivizumab in Cotton Rats by Respiratory Syncytial Virus Mutants
Zhao, X., Chen, F., Megaw, A. G., et al. (2004) · The Journal of Infectious Diseases · doi:10.1086/425515 · Cited by 49 · see citing works
Electron Cryomicroscopy Reveals Different F1+F2 Protein States in Intact Parainfluenza Virions
Ludwig, K., Schade, B., Böttcher, C., et al. (2008) · Journal of Virology · doi:10.1128/jvi.02154-07 · Cited by 32 · see citing works
Sastre, P., Melero, J. A., García‐Barreno, B., et al. (2005) · Journal of Medical Virology · doi:10.1002/jmv.20349 · Cited by 29 · see citing works
Self-citationSilva, L. M. D., & Siu, I. (1990) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1990.tb125434.x · Cited by 29 · see citing works
Toiron, C., López, J. A., Rivas, G., Andreu, D., Melero, J. A., & Bruix, M. (1998) · Biopolymers · doi:10.1002/(sici)1097-0282(199610)39:4 · Cited by 15 · see citing works
Self-citationSastre, P., Melero, J. A., García‐Barreno, B., et al. (2004) · Vaccine · doi:10.1016/j.vaccine.2004.06.023 · Cited by 13 · see citing works
Self-citationRespiratory Syncytial Virus Immune Globulin
Simões, E. A. F. (1997) · BioDrugs · doi:10.2165/00063030-199708020-00010 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Collins PL, Crowe JE (2007) Respiratory syncytial virus and metapneumovirus. Fields Virology (Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia), 5th Ed, pp 1601-1646.
Cited by
Sorted by citations
Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus
McLellan, J. S., Chen, M., Joyce, M. G., Sastry, M., Stewart-Jones, G. B. E., Yang, Y., Zhang, B., Chen, L., Srivatsan, S., Zheng, A., et al. (2013) · Science · doi:10.1126/science.1243283 · Cited by 1,126 · see citing works
Structure of RSV Fusion Glycoprotein Trimer Bound to a Prefusion-Specific Neutralizing Antibody
McLellan, J. S., Chen, M., Leung, S., Graepel, K. W., Du, X., Yang, Y., Zhou, T., Baxa, U., Yasuda, E., Beaumont, T., et al. (2013) · Science · doi:10.1126/science.1234914 · Cited by 883 · see citing works
A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism
Krarup, A., Truan, D., Furmanova-Hollenstein, P., Bogaert, L., Bouchier, P., Bisschop, I. J. M., Widjojoatmodjo, M. N., Zahn, R., Schuitemaker, H., McLellan, J. S., et al. (2015) · Nature Communications · doi:10.1038/ncomms9143 · Cited by 383 · see citing works
A proof of concept for structure-based vaccine design targeting RSV in humans
Crank, M. C., Ruckwardt, T. J., Chen, M., Morabito, K. M., Phung, E., Costner, P. J., Holman, L. A., Hickman, S. P., Berkowitz, N. M., Gordon, I. J., et al. (2019) · Science · doi:10.1126/science.aav9033 · Cited by 333 · see citing works
Espeseth, A. S., Cejas, P. J., Citron, M. P., Wang, D., DiStefano, D. J., Callahan, C., Donnell, G. O., Galli, J. D., Swoyer, R., Touch, S., et al. (2020) · npj Vaccines · doi:10.1038/s41541-020-0163-z · Cited by 190 · see citing works
Immunological Lessons from Respiratory Syncytial Virus Vaccine Development
Ruckwardt, T. J., Morabito, K. M., & Graham, B. S. (2019) · Immunity · doi:10.1016/j.immuni.2019.08.007 · Cited by 185 · see citing works
Aliprantis, A. O., Shaw, C. A., Griffin, P., Farinola, N., Railkar, R. A., Cao, X., Liu, W., Sachs, J. R., Swenson, C. J., Lee, H., et al. (2021) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2020.1829899 · Cited by 149 · see citing works
Structural vaccinology starts to deliver
Dormitzer, P. R., Grandi, G., & Rappuoli, R. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2893 · Cited by 143 · see citing works
Vaccines against human respiratory syncytial virus in clinical trials, where are we now?
Rossey, I., & Saelens, X. (2019) · Expert Review of Vaccines · doi:10.1080/14760584.2019.1675520 · Cited by 32 · see citing works
- Authors
- Magro, M., Mas, V., Chappell, K., Vázquez, M., Cano, O., Luque, D., Terrón, M. C., Melero, J. A., & Palomo, C.
- Affiliations
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (ES)
- Biología Viral, Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, 28220 Madrid, Spain; and
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Melero, José A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-02-08
- Volume
- 109
- Issue
- 8
- Pages
- 3089-3094
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3286924
- OpenAlex
- W1988459634
- Cited by
- 271
- References
- 33
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 25 · 2023: 23 · 2022: 13 · 2021: 18 · 2020: 19 · 2019: 23 · 2018: 18 · 2017: 25 · 2016: 21 · 2015: 24 · 2014: 13 · 2013: 14 · 2012: 2
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Ciencia e Innovación (SAF2009-11632)
- Topics
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- respiratory syncytial virus, F glycoprotein, prefusion conformation, neutralizing antibodies, postfusion conformation, palivizumab, RSV vaccine development, pediatric respiratory infection, prophylaxis
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Viral, Humans, Immunization, Molecular Sequence Data, Rabbits, Recombinant Proteins, Vaccinia virus, Viral Fusion Proteins, Respiratory Syncytial Virus, Human, Respiratory Syncytial Virus Infections, Protein Stability, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
