Stepwise conformational stabilization of a HIV-1 clade C consensus envelope trimer immunogen impacts vaccine-induced antibody responses

July 6, 2021

Hauser, A., Carnell, G., Held, K., et al.

Vaccines 2021, vol: 9(7) doi: 10.3390/vaccines9070750

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.

View Publication

Topics: Prometheus, nanoDSF, Virology, Publications

Previous Video
Automate your screening workflow for characterizing protein stability
Automate your screening workflow for characterizing protein stability

Up next
How Merck KGaA uses light scattering measurements for better developability assessment of biologic therapeutics
How Merck KGaA uses light scattering measurements for better developability assessment of biologic therapeutics

Ready to tackle your challenging stability characterizations?

Discover tools