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TitleTargeting HIV Env immunogens to B cell follicles in nonhuman primates through immune complex or protein nanoparticle formulations.
Journal, issue, pagesNPJ Vaccines, Vol. 5, Issue 1, Page 72, Year 2020
Publish dateAug 5, 2020
AuthorsJacob T Martin / Christopher A Cottrell / Aleksandar Antanasijevic / Diane G Carnathan / Benjamin J Cossette / Chiamaka A Enemuo / Etse H Gebru / Yury Choe / Federico Viviano / Stephanie Fischinger / Talar Tokatlian / Kimberly M Cirelli / George Ueda / Jeffrey Copps / Torben Schiffner / Sergey Menis / Galit Alter / William R Schief / Shane Crotty / Neil P King / David Baker / Guido Silvestri / Andrew B Ward / Darrell J Irvine /
PubMed AbstractFollowing 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 ...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.
External linksNPJ Vaccines / PubMed:32802411 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 4.6 Å
Structure data

21227

6vkn

EMDB-21227, PDB-6vkn:
BG505 SOSIP.v5.2.N241.N289 in complex with rhesus macaque Fab RM19R
Method: EM (single particle) / Resolution: 3.7 Å

21230

6vl5

EMDB-21230, PDB-6vl5:
BG505 SOSIP reconstructed from a designed tetrahedral nanoparticle, BG505 SOSIP-T33_dn2
Method: EM (single particle) / Resolution: 4.5 Å

21231

6vl6

EMDB-21231, PDB-6vl6:
De novo designed tetrahedral nanoparticle T33_dn2 presenting BG505 SOSIP trimers
Method: EM (single particle) / Resolution: 4.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
  • synthetic construct (others)
KeywordsVIRAL PROTEIN/Immune System / HIV / antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / DE NOVO PROTEIN / HIV Env / de novo / nanoparticles / vaccine design

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