Hauser, Alexandra and Carnell, George and Held, Kathrin and Sulbaran, Guidenn and Tischbierek, Nadine and Rogers, Lisa and Pollakis, Georgios and Tonks, Paul and Hoelscher, Michael and Ding, Song and Sanders, Rogier W. and Geldmacher, Christof and Sattentau, Quentin and Weissenhorn, Winfried and Heeney, Jonathan L. and Peterhoff, David and Wagner, Ralf (2021) Stepwise Conformational Stabilization of a HIV-1 Clade C Consensus Envelope Trimer Immunogen Impacts the Profile of Vaccine-Induced Antibody Responses. VACCINES, 9 (7): 750. ISSN , 2076-393X
Full text not available from this repository. (Request a copy)Abstract
Stabilization of the HIV-1 Envelope glycoprotein trimer (Env) in its native pre-fusion closed conformation is regarded as one of several requirements for the induction of neutralizing antibody (nAb) responses, which, in turn, will most likely be a prerequisite for the development of an efficacious preventive vaccine. Here, we systematically analyzed how the stepwise stabilization of a clade C consensus (ConC) Env immunogen impacts biochemical and biophysical protein traits such as antigenicity, thermal stability, structural integrity, and particle size distribution. The increasing degree of conformational rigidification positively correlates with favorable protein characteristics, leading to optimized homogeneity of the protein preparations, increased thermal stability, and an overall favorable binding profile of structure-dependent broadly neutralizing antibodies (bnAbs) and non-neutralizing antibodies (non-nAbs). We confirmed that increasing the structural integrity and stability of the Env trimers positively correlates with the quality of induced antibody responses by the immunogens. These and other data contribute to the selection of ConCv5 KIKO as novel Env immunogens for use within the European Union's H2020 Research Consortium EHVA (European HIV Alliance) for further preclinical analysis and phase 1 clinical development.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLYCOPROTEIN COMPLEX; ENV; DIVERSITY; PROTEIN; EPITOPE; DESIGN; BROAD; 2G12; HIV vaccine; envelope; stabilized trimer; clade C; consensus; centralized sequence; immunization; immunogen design; antibody response; peptide microarray |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Sep 2022 05:34 |
| Last Modified: | 12 Sep 2022 05:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47045 |
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