Targeting HIV Env immunogens to B cell follicles in nonhuman primates through immune complex or protein nanoparticle formulations.
HIV infections
Innate immunity
Protein vaccines
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
2020
2020
Historique:
received:
17
02
2020
accepted:
11
06
2020
entrez:
18
8
2020
pubmed:
18
8
2020
medline:
18
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32802411
doi: 10.1038/s41541-020-00223-1
pii: 223
pmc: PMC7406516
doi:
Types de publication
Journal Article
Langues
eng
Pagination
72Subventions
Organisme : NIAID NIH HHS
ID : F31 AI131873
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Informations de copyright
© The Author(s) 2020.
Déclaration de conflit d'intérêts
Competing interestsD.B. and G.U. are inventors on US patent application 62/422,872 titled “Computational design of self-assembling cyclic protein homo-oligomers”. D.B., N.P.K., and G.U. are inventors on US patent application 62/636,757 titled “Method of multivalent antigen presentation on designed protein nanomaterials”. N.P.K. and D.B. are co-founders and shareholders in Icosavax, a company that has licensed these patent applications, and N.P.K. is a member of Icosavax’s Scientific Advisory Board. All other authors declare no competing interests.
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