Intranasal vaccination with influenza HA/GO-PEI nanoparticles provides immune protection against homo- and heterologous strains

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.

Airway Exposure to Polyethyleneimine Nanoparticles Induces Type 2 Immunity by a Mechanism Involving Oxidative Stress and ATP Release

“…More recently, PEI was shown to exhibit robust mucosal adjuvanticity and protective immunity against influenza and herpes simplex virus-2 when administered intranasally with hemagglutinin or glycoprotein D antigens co-formulated with PEI [65]. Moreover, when branched PEI was used for surface functionalization of a graphene oxide (GO) based vaccine delivery vector, enhanced interactions between GO and recombinant influenza hemagglutinin (HA) occurred that resulted in positively charged nanoparticles with mucosal adjuvant activity [66]. Intranasal administration of GO-HA nanoparticles, in the absence of any additional adjuvants, stimulated robust, antigen specific immune responses that were protective against homologous and heterologous influenza viruses.…”

Rapid and Efficient Testing of The Toxicity of Graphene-Related Materials in Primary Human Lung Cells

“…Exposure to graphene is variable during its production process, involving direct interaction with the respiratory tract if adequate personal protective equipment is not used [54]. Concerns about the toxic effect of graphene on the lungs also extend to its integration into everyday products such as face masks [50] and biomedical applications such as intranasal immunization [55]. Moreover, different studies on the biodistribution of graphene have demonstrated the presence of graphene in the lung after intravenous [56,57], oral [58], and intraperitoneal administration [59,60].…”

Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats

“…[ 149,150 ] We recently fabricated a polyethyleneimine (PEI)‐functionalized GO (GP) influenza vaccine that significantly boosted influenza HA immunogenicity following intranasal immunization. [ 99 ] This GP‐HA nanoparticle immunization induced robust antibody and cellular responses in mice, protecting mice against homologous and heterologous influenza viruses.…”

“…[ 157 ] PEI‐functionalized GP‐HA nanoparticles demonstrated potent cross‐reactive immune responses at systemic and mucosal sites, providing homo‐ and heterologous immune protection in mice. [ 99 ]…”

“…Nanoparticle platforms have shown advantages in overcoming the shortage of conventional vaccines in inducing robust mucosal immune responses. [99][100][101][102] More advances regarding nanotechnology contributing to mucosal immunity will be further commented later.…”