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TitleHigh-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination.
Journal, issue, pagesElife, Vol. 10, Year 2021
Publish dateJan 13, 2021
AuthorsAdam S Dingens / Payal Pratap / Keara Malone / Sarah K Hilton / Thomas Ketas / Christopher A Cottrell / Julie Overbaugh / John P Moore / P J Klasse / Andrew B Ward / Jesse D Bloom /
PubMed AbstractMapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which ...Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.
External linksElife / PubMed:33438580 / PubMed Central
MethodsEM (single particle)
Resolution20.0 Å
Structure data

EMDB-23366:
Polyclonal Immune complex of Fab binding to BG505 SOSIP.664 from serum of rabbit 5724 at wk 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-23367:
Polyclonal Immune complex of Fab binding to BG505 SOSIP.664 from serum of rabbit 5727 at wk 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-23368:
Polyclonal Immune complex of Fab binding to BG505 SOSIP.v4.1 from serum of rabbit 2124 at wk 22
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-23369:
Polyclonal Immune complex of Fab binding to BG505 SOSIP.v4.1 from serum of rabbit 2214 at wk 43
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-23370:
Polyclonal Immune complex of Fab binding to BG505 SOSIP.v4.1 from serum of rabbit 2423 at wk 18
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-23371:
Polyclonal Immune complex of Fab binding to BG505 SOSIP.v4.1 from serum of rabbit 2425 at wk 18
Method: EM (single particle) / Resolution: 20.0 Å

Source
  • Oryctolagus cuniculus (rabbit)
  • Human immunodeficiency virus

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