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| Title | Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates. |
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| Journal, issue, pages | NPJ Vaccines, Vol. 7, Issue 1, Page 152, Year 2022 |
| Publish date | Nov 25, 2022 |
 Authors | E I M M Reiss / M M van Haaren / J van Schooten / M A F Claireaux / P Maisonnasse / A Antanasijevic / J D Allen / I Bontjer / J L Torres / W-H Lee / G Ozorowski / N Vázquez Bernat / M Kaduk / Y Aldon / J A Burger / H Chawla / A Aartse / M Tolazzi / H Gao / P Mundsperger / M Crispin / D C Montefiori / G B Karlsson Hedestam / G Scarlatti / A B Ward / R Le Grand / R Shattock / N Dereuddre-Bosquet / R W Sanders / M J van Gils /        |
| PubMed Abstract | The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a ...The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial consensus sequence of all HIV-1 isolates in group M. In preclinical studies ConM SOSIP.v7 trimers induced strong autologous NAb responses in non-human primates (NHPs). To fine-map these responses, we isolated monoclonal antibodies (mAbs) from six cynomolgus macaques that were immunized three times with ConM SOSIP.v7 protein and boosted twice with the closely related ConSOSL.UFO.664 immunogen. A total of 40 ConM and/or ConS-specific mAbs were isolated, of which 18 were retrieved after the three ConM SOSIP.v7 immunizations and 22 after the two immunizations with ConSOSL.UFO.664. 22 mAbs (55%) neutralized the ConM and/or ConS virus. Cross-neutralization of ConS virus by approximately one-third of the mAbs was seen prior to ConSOSL.UFO.664 immunization, albeit with modest potency. Neutralizing antibodies predominantly targeted the V1 and V2 regions of the immunogens, with an apparent extension towards the V3 region. Thus, the V1V2V3 region is immunodominant in the potent NAb response elicited by two consensus sequence native-like HIV-1 Env immunogens. Immunization with these soluble consensus Env proteins also elicited non-neutralizing mAbs targeting the trimer base. These results inform the use and improvement of consensus-based trimer immunogens in combinatorial vaccine strategies. |
 External links | NPJ Vaccines / PubMed:36433972 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 25.0 Å |
| Structure data |  EMDB-14888: CM01B in complex with ConM SOSIP  EMDB-14889: CM05A1 in complex with conM SOSIP  EMDB-14890: CM02A in complex with conM SOSIP  EMDB-14891: CM04F in complex with conM SOSIP  EMDB-14892: CM03B in complex with conM SOSIP  EMDB-14893: CM05E in complex with conM SOSIP  EMDB-14894: CM05L in complex with conM SOSIP  EMDB-14895: NHP MCM02 wk26 N355/N289 pAb in complex with ConM SOSIP  EMDB-14896: NHP MCM04 wk26 base pAb in complex with ConM SOSIP  EMDB-14897: NHP MCM04 wk26 N611 pAb in complex with ConM SOSIP  EMDB-14898: NHP MCM05 wk26 V1V2V3 and base pAbs in complex with ConM SOSIP  EMDB-14899: NHP MCM06 wk26 base and N611 pAbs in complex with ConS SOSIP  EMDB-14900: NHP MCM02 wk26 N355/N289 pAb in complex with ConS SOSIP  EMDB-14901: NHP CCK046 wk70 base pAb in complex with ConM SOSIP  EMDB-14902: NHP MCM06 wk70 N355/N289 pAb in complex with ConM SOSIP  EMDB-14903: NHP MCM06 wk70 N611 pAb in complex with ConM SOSIP  EMDB-14904: NHP MCM04 wk70 V1V2V3 pAb in complex with ConM SOSIP  EMDB-14905: NHP MCM03 wk70 base pAb in complex with ConS SOSIP  EMDB-14906: NHP MCM04 wk70 N611 pAb in complex with ConS SOSIP  EMDB-14907: NHP MCM04 wk70 V1V2V3 pAb in complex with ConS SOSIP  EMDB-14908: NHP MCM06 wk70 N355/N289 pAb in complex with ConS SOSIP |
| Source |
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Macaca fascicularis (crab-eating macaque)