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TitleA potently neutralizing and protective human antibody targeting antigenic site V on RSV and hMPV fusion glycoprotein.
Journal, issue, pagesCell Rep Med, Vol. 7, Issue 2, Page 102564, Year 2026
Publish dateFeb 17, 2026
AuthorsAlexandra A Abu-Shmais / Luqiang Guo / Ahmed Magdy Khalil / Sabina E Leonard / Rose J Miller / Alexis K Janke / Matthew J Vukovich / Lindsay E Bass / Yukthi P Suresh / Scott A Rush / Rachael M Wolters / Nurgun Kose / Robert H Carnahan / James E Crowe / Rachel H Bonami / Jarrod J Mousa / Jason S McLellan / Ivelin S Georgiev /
PubMed AbstractHuman respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are frequent drivers of morbidity and mortality in susceptible populations. The primary target of neutralizing antibodies is ...Human respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are frequent drivers of morbidity and mortality in susceptible populations. The primary target of neutralizing antibodies is the fusion (F) glycoprotein on the surface of the RSV and hMPV virion. As a result of the structural conservation between RSV and hMPV F, three antigenic regions are known to induce cross-neutralizing responses: sites III, IV, and V. Leveraging LIBRA-seq, we identify five RSV/hMPV cross-reactive human antibodies. One antibody, RM 5-1, potently neutralizes all tested viruses from the major subgroups of RSV and hMPV and provides protection against RSV and hMPV in a mouse challenge model. Structural analysis reveals that RM 5-1 utilizes an uncommon genetic signature to bind an epitope that spans sites Ø, II, and V. These findings highlight the molecular and structural elements influencing RSV and hMPV cross-reactivity as well as the potential of antibody RM 5-1 for translational development.
External linksCell Rep Med / PubMed:41547352 / PubMed Central
MethodsEM (single particle)
Resolution4.24 Å
Structure data

EMDB-45412, PDB-9cb1:
Cryo-EM Structure of the Human Neutralizing Antibody 5-1 in Complex with Prefusion Human Metapneumovirus F Glycoprotein
Method: EM (single particle) / Resolution: 4.24 Å

Source
  • human metapneumovirus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / hMPV F / 5-1 antibody / antibody / VIRAL PROTEIN-IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex

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