Bartek 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 Abstract
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 ...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.
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
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