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TitleMapping Polyclonal Antibody Responses in Non-human Primates Vaccinated with HIV Env Trimer Subunit Vaccines.
Journal, issue, pagesCell Rep, Vol. 30, Issue 11, Page 3755-33765.e7, Year 2020
Publish dateMar 17, 2020
AuthorsBartek Nogal / Matteo Bianchi / Christopher A Cottrell / Robert N Kirchdoerfer / Leigh M Sewall / Hannah L Turner / Fangzhu Zhao / Devin Sok / Dennis R Burton / Lars Hangartner / Andrew B Ward /
PubMed AbstractRational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target ...Rational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target responses. Here, we use our electron microscopy polyclonal epitope mapping approach to describe the antibody specificities elicited by immunization of non-human primates with soluble HIV envelope trimers and subsequent repeated viral challenge. An increased diversity of epitopes recognized and the approach angle by which these antibodies bind constitute a hallmark of the humoral response in most protected animals. We also show that fusion peptide-specific antibodies are likely responsible for some neutralization breadth. Moreover, cryoelectron microscopy (cryo-EM) analysis of a fully protected animal reveals a high degree of clonality within a subset of putatively neutralizing antibodies, enabling a detailed molecular description of the antibody paratope. Our results provide important insights into the immune response against a vaccine candidate that entered into clinical trials in 2019.
External linksCell Rep / PubMed:32187547 / PubMed Central
MethodsEM (single particle)
Resolution3.87 - 32.8 Å
Structure data

20396

6v0r

EMDB-20396: Cryo-EM Reconstruction of Polyclonal Serum Fab From a Protected Rhesus Macaque Complexed with BG505 SOSIP.664
PDB-6v0r: BG505 SOSIP.664 Trimer
Method: EM (single particle) / Resolution: 3.87 Å

EMDB-20399:
Unimmunized control rhesus macaque BZ05 (challenged with SHIV) serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 16.4 Å

EMDB-20400:
Unimmunized control rhesus macaque BZ11 (challenged with SHIV) serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-20401:
Unimmunized control rhesus macaque BZ13 (challenged with SHIV) serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 32.8 Å

EMDB-20402:
BG505-immunized rhesus macaque 12-060 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 22.7 Å

EMDB-20403:
BG505-immunized rhesus macaque 12-065 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-20404:
BG505-immunized rhesus macaque OQ7 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-20405:
BG505-immunized rhesus macaque 12-153 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-20409:
BG505-immunized rhesus macaque 12M-248 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 28.7 Å

EMDB-20410:
BG505-immunized rhesus macaque 12-149 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 29.5 Å

EMDB-20415:
BG505-immunized rhesus macaque 12-143 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 16.4 Å

EMDB-20423:
BG505-immunized rhesus macaque 12-137 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 12.8 Å

EMDB-20424:
BG505-immunized rhesus macaque 12M-169 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 18.45 Å

EMDB-20425:
BG505-immunized rhesus macaque 11M-088 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-20426:
BG505-immunized rhesus macaque 12-046 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 15.6 Å

EMDB-20427:
BG505-immunized rhesus macaque 4O9 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 16.4 Å

EMDB-20428:
BG505-immunized rhesus macaque 12-137 wk 10 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 19.7 Å

EMDB-20429:
BG505-immunized rhesus macaque 11M-088 wk 12 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 17.4 Å

EMDB-20884:
Negative-stain EM map of BG505-immunized rhesus macaque 12-084 wk 28 serum fab complexed with BG505 SOSIP trimer
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-20885:
Negative-stain EM map of BG505-immunized rhesus macaque 12-046 wk 26 serum fab complexed with 25710
Method: EM (single particle) / Resolution: 29.5 Å

EMDB-20886:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 4O9 wk 26 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20887:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 4O9 wk 26 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20888:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 4O9 wk 10 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20889:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 4O9 wk 10 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20890:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 4O9 wk 10 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20891:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 11M-088 wk 28 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20892:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 11M-088 wk 28 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20893:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 11M-088 wk 12 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20894:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 11M-088 wk 12 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 25.5 Å

EMDB-20895:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 11M-088 wk 12 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20896:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-137 wk 28 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.0 Å

EMDB-20897:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-137 wk 28 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-20898:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-137 wk 28 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20899:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-137 wk 10 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20921:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-046 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20936:
Negative-stain EM map of BG505-immunized rhesus macaque 12-137 wk 26 serum fab complexed with 398F1 SOSIP.664
Method: EM (single particle) / Resolution: 22.7 Å

EMDB-20937:
Negative-stain EM map of BG505-immunized rhesus macaque 12-046 wk 26 serum fab complexed with 398F1 SOSIP.664
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-20938:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-065 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20939:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque OQ7 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 27.0 Å

EMDB-20940:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque OQ7 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 27.0 Å

EMDB-20941:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-143 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 22.5 Å

EMDB-20942:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-046 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 22.5 Å

EMDB-20943:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-046 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-20944:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-137 wk 10 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 22.5 Å

EMDB-20946:
BG505-immunized rhesus macaque 12-137 wk 28 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20970:
BG505-immunized rhesus macaque 11M088 wk 28 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-20971:
BG505-immunized rhesus macaque 4O9 wk 10 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-20972:
BG505-immunized rhesus macaque 4O9 wk 26 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-20973:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ05 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-20974:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ05 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20975:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ05 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.7 Å

EMDB-20976:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ11 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.0 Å

EMDB-20977:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ11 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-20978:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ11 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.7 Å

EMDB-20979:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ13 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-20980:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ13 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20981:
Negative-stain EM map from 3D sorting of unimmunized control rhesus macaque BZ13 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20982:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-060 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20983:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-060 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 22.5 Å

EMDB-20984:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-065 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-20985:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-065 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20987:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-143 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 26.5 Å

EMDB-20988:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-143 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 22.5 Å

EMDB-20989:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 12-137 wk 0 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-20990:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 11M-088 wk 28 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20991:
Negative-stain EM map from 3D sorting of BG505-immunized rhesus macaque 4O9 wk 26 serum fab complexed with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-20992:
Negative-stain EM map of BG505-immunized rhesus macaque 12-084 wk 26 serum fab complexed with 398F1 SOSIP.664
Method: EM (single particle) / Resolution: 22.5 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • Macaca mulatta (Rhesus monkey)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / antibody / HIV / glycoprotein / polyclonal / non-human primate / rhesus macaque

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