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Publications

Journal Article Research Support, N.I.H., Extramural Epublish 2 citations

PubMed: 39240547 DOI: 10.1039/d4nh00287c

Double-layered protein nanoparticles conjugated with truncated flagellin induce improved mucosal and systemic immune responses in mice.

Nanoscale Horiz 9(11):2016-2030

Authors: Joo Kyung Kim, Wandi Zhu, Chunhong Dong, Lai Wei, Yao Ma, Timothy Denning, Sang-Moo Kang, Bao-Zhong Wang

Affiliations

  • Center for Inflammation, Immunity & Infection, Georgia State University Institute for Biomedical Sciences, 100 Piedmont Ave SE, Atlanta, Georgia 30303, USA.

Abstract

Influenza viral infection poses a severe risk to global public health. Considering the suboptimal protection provided by current influenza vaccines against circulating influenza A viruses, it is imperative to develop novel vaccine formulations to combat respiratory infections. Here, we report the development of an intranasally-administered, self-adjuvanted double-layered protein nanoparticle consisting of influenza nucleoprotein (NP) cores coated with hemagglutinin (HA) and a truncated form of bacterial flagellin (tFliC). Intranasal vaccination of these nanoparticles notably amplified both antigen-specific humoral and cellular immune responses in the systematic compartments. Elevated antigen-specific IgA and IgG levels in mucosal washes, along with increased lung-resident memory B cell populations, were observed in the respiratory system of the immunized mice. Furthermore, intranasal vaccination of tFliC-adjuvanted nanoparticles enhanced survival rates against homologous and heterologous H3N2 viral challenges. Intriguingly, mucosal slow delivery of the prime dose (by splitting the dose into 5 applications over 8 days) significantly enhanced germinal center reactions and effector T-cell populations in lung draining lymph nodes, therefore promoting the protective efficacy against heterologous influenza viral challenges compared to single-prime immunization. These findings highlight the potential of intranasal immunization with tFliC-adjuvanted protein nanoparticles to bolster mucosal and systemic immune responses, with a slow-delivery strategy offering a promising approach for combating influenza epidemics.

MeSH

Cells, Flagellin, Lung, Immunization, Vaccines, Nanoparticles, Vaccination, Influenza, Human, Immunity, Nanotechnology, Infections

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