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Intranasal vaccination with influenza HA/GO-PEI nanoparticles provides immune protection against homo- and heterologous strains.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 May 11; Vol. 118 (19). - Publication Year :
- 2021
-
Abstract
- Intranasal (i.n.) immunization is a promising vaccination route for infectious respiratory diseases such as influenza. Recombinant protein vaccines can overcome the safety concerns and long production phase of virus-based influenza vaccines. However, soluble protein vaccines are poorly immunogenic if administered by an i.n. route. Here, we report that polyethyleneimine-functionalized graphene oxide nanoparticles (GP nanoparticles) showed high antigen-loading capacities and superior immunoenhancing properties. Via a facile electrostatic adsorption approach, influenza hemagglutinin (HA) was incorporated into GP nanoparticles and maintained structural integrity and antigenicity. The resulting GP nanoparticles enhanced antigen internalization and promoted inflammatory cytokine production and JAWS II dendritic cell maturation. Compared with soluble HA, GP nanoparticle formulations induced significantly enhanced and cross-reactive immune responses at both systemic sites and mucosal surfaces in mice after i.n. immunization. In the absence of any additional adjuvant, the GP nanoparticle significantly boosted antigen-specific humoral and cellular immune responses, comparable to the acknowledged potent mucosal immunomodulator CpG. The robust immune responses conferred immune protection against challenges by homologous and heterologous viruses. Additionally, the solid self-adjuvant effect of GP nanoparticles may mask the role of CpG when coincorporated. In the absence of currently approved mucosal adjuvants, GP nanoparticles can be developed into potent i.n. influenza vaccines, providing broad protection. With versatility and flexibility, the GP nanoplatform can be easily adapted for constructing mucosal vaccines for different respiratory pathogens.<br />Competing Interests: The authors declare no competing interest.<br /> (Copyright © 2021 the Author(s). Published by PNAS.)
- Subjects :
- Administration, Intranasal
Animals
Cell Line
Cytokines immunology
Cytokines metabolism
Female
Graphite chemistry
Graphite immunology
Hemagglutinin Glycoproteins, Influenza Virus chemistry
Hemagglutinin Glycoproteins, Influenza Virus immunology
Humans
Immunity, Humoral drug effects
Immunity, Humoral immunology
Immunity, Mucosal drug effects
Immunity, Mucosal immunology
Influenza A Virus, H3N2 Subtype drug effects
Influenza A Virus, H3N2 Subtype physiology
Influenza Vaccines administration & dosage
Influenza Vaccines chemistry
Influenza, Human prevention & control
Influenza, Human virology
Mice, Inbred BALB C
Nanoparticles administration & dosage
Oligodeoxyribonucleotides chemistry
Oligodeoxyribonucleotides immunology
Orthomyxoviridae Infections prevention & control
Orthomyxoviridae Infections virology
Polyethyleneimine chemistry
Vaccination methods
Mice
Cross Reactions immunology
Influenza A Virus, H3N2 Subtype immunology
Influenza Vaccines immunology
Influenza, Human immunology
Nanoparticles chemistry
Orthomyxoviridae Infections immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 118
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 33941704
- Full Text :
- https://doi.org/10.1073/pnas.2024998118