Maliqi, Liridona and Friedrich, Nikolas and Glogl, Matthias and Schmutz, Stefan and Schmidt, Daniel and Rusert, Peter and Schanz, Merle and Zaheri, Maryam and Pasin, Chloe and Niklaus, Cyrille and Foulkes, Caio and Reinberg, Thomas and Dreier, Birgit and Abela, Irene and Peterhoff, David and Hauser, Alexandra and Kouyos, Roger D. and Guenthard, Huldrych F. and van Gils, Marit J. and Sanders, Rogier W. and Wagner, Ralf and Plueckthun, Andreas and Trkola, Alexandra (2023) Assessing immunogenicity barriers of the HIV-1 envelope trimer. NPJ VACCINES, 8 (1): 148. ISSN , 2059-0105
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BROADLY NEUTRALIZING ANTIBODIES; MEMORY B-CELLS; REPEAT PROTEINS; RIBOSOME DISPLAY; RAPID SELECTION; AFFINITY; RESPONSES; BINDERS; COEVOLUTION; MATURATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Mar 2024 14:17 |
| Last Modified: | 13 Mar 2024 14:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59969 |
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