학술논문
Assessing immunogenicity barriers of the HIV-1 envelope trimer
Document Type
article
Author
Liridona Maliqi; Nikolas Friedrich; Matthias Glögl; Stefan Schmutz; Daniel Schmidt; Peter Rusert; Merle Schanz; Maryam Zaheri; Chloé Pasin; Cyrille Niklaus; Caio Foulkes; Thomas Reinberg; Birgit Dreier; Irene Abela; David Peterhoff; Alexandra Hauser; Roger D. Kouyos; Huldrych F. Günthard; Marit J. van Gils; Rogier W. Sanders; Ralf Wagner; Andreas Plückthun; Alexandra Trkola
Source
npj Vaccines, Vol 8, Iss 1, Pp 1-14 (2023)
Subject
Language
English
ISSN
2059-0105
Abstract
Abstract Understanding the balance between epitope shielding and accessibility on HIV-1 envelope (Env) trimers is essential to guide immunogen selection for broadly neutralizing antibody (bnAb) based vaccines. To investigate the antigenic space of Env immunogens, we created a strategy based on synthetic, high diversity, Designed Ankyrin Repeat Protein (DARPin) libraries. We show that DARPin Antigenicity Analysis (DANA), a purely in vitro screening tool, has the capability to extrapolate relevant information of antigenic properties of Env immunogens. DANA screens of stabilized, soluble Env trimers revealed that stronger trimer stabilization led to the selection of highly mutated DARPins with length variations and framework mutations mirroring observations made for bnAbs. By mimicking heterotypic prime-boost immunization regimens, DANA may be used to select immunogen combinations that favor the selection of trimer-reactive binders. This positions DANA as a versatile strategy for distilling fundamental antigenic features of immunogens, complementary to preclinical immunogenicity testing.