Mosaic quadrivalent influenza vaccine single nanoparticle characterization

Author:

Yang, Rong Sylvie

Traver, Maria

Barefoot, Nathan

Stephens, Tyler

Alabanza, Casper

Manzella-Lapeira, Javier

Zou, Guozhang

Wolff, Jeremy

Li, Yile

Resto, Melissa

Shadrick, William

Yang, Yanhong

Ivleva, Vera B

Tsybovsky,Yaroslav

Carlton, Kevin

Brzostowski, Joseph

Gall, Jason G

Lei, Q Paula
Author Address

Vaccine Production Program, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd., Gaithersburg, MD, 20878, USA., Twinbrook Imaging Facility, LIG, NIAID, NIH, Gaithersburg, MD, USA., Vaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Vaccine Production Program, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd., Gaithersburg, MD, 20878, USA. paula.lei@nih.gov.,

Abstract:

Recent work by our laboratory and others indicates that co-display of multiple antigens on protein-based nanoparticles may be key to induce cross-reactive antibodies that provide broad protection against disease. To reach the ultimate goal of a universal vaccine for seasonal influenza, a mosaic influenza nanoparticle vaccine (FluMos-v1) was developed for clinical trial (NCT04896086). FluMos-v1 is unique in that it is designed to co-display four recently circulating haemagglutinin (HA) strains; however, current vaccine analysis techniques are limited to nanoparticle population analysis, thus, are unable to determine the valency of an individual nanoparticle. For the first time, we demonstrate by total internal reflection fluorescence microscopy and supportive physical-chemical methods that the co-display of four antigens is indeed achieved in single nanoparticles. Additionally, we have determined percentages of multivalent (mosaic) nanoparticles with four, three, or two HA proteins. The integrated imaging and physicochemical methods we have developed for single nanoparticle multivalency will serve to further understand immunogenicity data from our current FluMos-v1 clinical trial. © 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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