Double-layered protein nanoparticles conjugated with truncated flagellin induce improved mucosal and systemic immune responses in mice.
Nanoscale Horiz
; 2024 Sep 06.
Article
em En
| MEDLINE
| ID: mdl-39240547
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Nanoscale Horiz
/
Nanoscale horiz. (Online)
/
Nanoscale horizons (Online)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos