Journal article

Self-assembling influenza nanoparticle vaccines drive extended germinal center activity and memory B cell maturation.

Hannah G Kelly, Hyon-Xhi Tan, Jennifer A Juno, Robyn Esterbauer, Yi Ju, Wenbo Jiang, Verena C Wimmer, Brigette C Duckworth, Joanna R Groom, Frank Caruso, Masaru Kanekiyo, Stephen J Kent, Adam K Wheatley

JCI Insight | American Society for Clinical Investigation | Published : 2020

Abstract

Protein-based, self-assembling nanoparticles elicit superior immunity compared with soluble protein vaccines, but the immune mechanisms underpinning this effect remain poorly defined. Here, we investigated the immunogenicity of a prototypic ferritin-based nanoparticle displaying influenza hemagglutinin (HA) in mice and macaques. Vaccination of mice with HA-ferritin nanoparticles elicited higher serum antibody titers and greater protection against experimental influenza challenge compared with soluble HA protein. Germinal centers in the draining lymph nodes were expanded and persistent following HA-ferritin vaccination, with greater deposition of antigen that colocalized with follicular dendr..

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Grants

Awarded by ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Project


Awarded by NHMRC


Funding Acknowledgements

The authors acknowledge the facilities and the scientific and technical assistance of the Biological Optical Microscopy Platform, the University of Melbourne. We also thank the expertise of Melbourne Cytometry Platform, specifically Vanta Jameson and Sarvy Taghavi. TEM analyses were conducted using the facilities at Bio21 Advanced Microscopy Facility, the University of Melbourne. HAI assay reagents and advice were provided by Paul Whitney, World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, and Mingyang Wang, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, the University of Melbourne. The following reagent was obtained through BEI Resources, NIAID, NIH: Peptide Array, Influenza Virus A/Puerto Rico/8/1934 (H1N1) Hemagglutinin Protein, NR-18973. This study was supported by the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Project CE140100036 (to SJK and FC), an NHMRC program grant APP1149990 (to SJK), and NHMRC project grants GNT1129099 and GNT1162760 (to AKW). JAJ, FC, SJK, and AKW are supported by NHMRC fellowships.