Hauser, Alexandra, Carnell, George, Held, Kathrin, Sulbaran, Guidenn, Tischbierek, Nadine, Rogers, Lisa, Pollakis, Georgios 
ORCID: 0000-0002-9659-5461, Tonks, Paul, Hoelscher, Michael, Ding, Song et al (show 7 more authors)
(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-.
|
Text
Stepwise Conformational Stabilization of a HIV-1 Clade C Consensus Envelope Trimer Immunogen Impacts the Profile of Vaccine-.pdf - Published version Download (32MB) | Preview |
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: | HIV vaccine, envelope, stabilized trimer, clade C, consensus, centralized sequence, immunization, immunogen design, antibody response, peptide microarray |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 01 Oct 2021 10:15 |
| Last Modified: | 18 Jan 2023 21:27 |
| DOI: | 10.3390/vaccines9070750 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3138926 |
Dimensions
Dimensions
