6VL6

De novo designed tetrahedral nanoparticle T33_dn2 presenting BG505 SOSIP trimers

Summary for 6VL6

• Entry DOI: 10.2210/pdb6vl6/pdb
• EMDB information: 21231
• Descriptor: T33_dn2A, T33_dn2B (2 entities in total)
• Functional Keywords: hiv env, de novo, nanoparticles, vaccine design, de novo protein
• Biological source: synthetic construct; More
• Total number of polymer chains: 24
• Total formula weight: 348506.82

Authors

Ward, A.B.,Antanasijevic, A. (deposition date: 2020-01-22, release date: 2020-08-12, Last modification date: 2024-03-06)

Primary citation

Martin, J.T.,Cottrell, C.A.,Antanasijevic, A.,Carnathan, D.G.,Cossette, B.J.,Enemuo, C.A.,Gebru, E.H.,Choe, Y.,Viviano, F.,Fischinger, S.,Tokatlian, T.,Cirelli, K.M.,Ueda, G.,Copps, J.,Schiffner, T.,Menis, S.,Alter, G.,Schief, W.R.,Crotty, S.,King, N.P.,Baker, D.,Silvestri, G.,Ward, A.B.,Irvine, D.J.
Targeting HIV Env immunogens to B cell follicles in nonhuman primates through immune complex or protein nanoparticle formulations.
NPJ Vaccines, 5:72-72, 2020

PubMed Abstract: Following immunization, high-affinity antibody responses develop within germinal centers (GCs), specialized sites within follicles of the lymph node (LN) where B cells proliferate and undergo somatic hypermutation. Antigen availability within GCs is important, as B cells must acquire and present antigen to follicular helper T cells to drive this process. However, recombinant protein immunogens such as soluble human immunodeficiency virus (HIV) envelope (Env) trimers do not efficiently accumulate in follicles following traditional immunization. Here, we demonstrate two strategies to concentrate HIV Env immunogens in follicles, via the formation of immune complexes (ICs) or by employing self-assembling protein nanoparticles for multivalent display of Env antigens. Using rhesus macaques, we show that within a few days following immunization, free trimers were present in a diffuse pattern in draining LNs, while trimer ICs and Env nanoparticles accumulated in B cell follicles. Whole LN imaging strikingly revealed that ICs and trimer nanoparticles concentrated in as many as 500 follicles in a single LN within two days after immunization. Imaging of LNs collected seven days postimmunization showed that Env nanoparticles persisted on follicular dendritic cells in the light zone of nascent GCs. These findings suggest that the form of antigen administered in vaccination can dramatically impact localization in lymphoid tissues and provides a new rationale for the enhanced immune responses observed following immunization with ICs or nanoparticles.

PubMed: 32802411
DOI: 10.1038/s41541-020-00223-1

Experimental method

ELECTRON MICROSCOPY (4.6 Å)