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TitleFoot-and-mouth disease virus antigenic landscape and reduced immunogenicity elucidated in atomic detail.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 8774, Year 2024
Publish dateOct 10, 2024
AuthorsHaozhou Li / Pan Liu / Hu Dong / Aldo Dekker / Michiel M Harmsen / Huichen Guo / Xiangxi Wang / Shiqi Sun /
PubMed AbstractUnlike most other picornaviruses, foot-and-mouth disease (FMD) intact virions (146S) dissociate easily into small pentameric subunits (12S). This causes a dramatically decreased immunogenicity by a ...Unlike most other picornaviruses, foot-and-mouth disease (FMD) intact virions (146S) dissociate easily into small pentameric subunits (12S). This causes a dramatically decreased immunogenicity by a mechanism that remains elusive. Here, we present the high-resolution structures of 12S (3.2 Å) and its immune complex of a single-domain antibody (VHH) targeting the particle interior (3.2 Å), as well as two 146S-specific VHHs complexed to distinct sites on the 146S capsid surface (3.6 Å and 2.9 Å). The antigenic landscape of 146S is depicted using 13 known FMD virus-antibody complexes. Comparison of the immunogenicity of 146S and 12S in pigs, focusing on the resulting antigenic sites and incorporating structural analysis, reveals that dissociation of 146S leads to structural alteration and destruction of multiple epitopes, resulting in significant differences in antibody profiles/lineages induced by 12S and 146S. Furthermore, 146S generates higher synergistic neutralizing antibody titers compared to 12S, whereas both particles induce similar total FMD virus specific antibody titers. This study can guide the structure-based rational design of novel multivalent and broad-spectrum recombinant vaccines for protection against FMD.
External linksNat Commun / PubMed:39389971 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.6 Å
Structure data

EMDB-34630, PDB-8hbg:
FMDV (A/TUR/14/98) in complex with M678F
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-34636, PDB-8hbi:
FMDV (A/TUR/14/98) in complex with M688F
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-34637, PDB-8hbj:
cocktail of FMDV (A/TUR/14/98) in complex with M678F and M688F
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-34689, PDB-8hee:
Pentamer of FMDV (A/TUR/14/98)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-34690, PDB-8heg:
Pentamer of FMDV (A/TUR/14/98) in complex with M3F
Method: EM (single particle) / Resolution: 3.2 Å

Source
  • foot-and-mouth disease virus a
  • lama glama (llama)
  • foot-and-mouth disease virus
KeywordsVIRUS / FMDV / antibody / VIRAL PROTEIN

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