Nasal delivery of H5N1 avian influenza vaccine formulated with GenJet™ or in vivo-jetPEI^®induces enhanced serological, cellular and protective immune responses

Abstract

Avian influenza virus infection is a serious public health threat and preventive vaccination is the most cost-effective public health intervention strategy. Unfortunately, currently available unadjuvanted avian influenza vaccines are poorly immunogenic and alternative vaccine formulations and delivery strategies are in urgent need to reduce the high risk of avian influenza pandemics. Cationic polymers have been widely used as vectors for gene delivery in vitro and in vivo. In this study, we formulated H5N1 influenza vaccines with GenJet™ or in vivo-jetPEI®, and showed that these formulations significantly enhanced the immunogenicity of H5N1 vaccines and conferred protective immunity in a mouse model. Detailed analyses of adaptive immune responses revealed that both formulations induced mixed TH1/TH2 antigen-specific CD4 T-cell responses, antigen-specific cytotoxic CD8 T-cell and memory B-cell responses. Our findings suggest that cationic polymers merit future development as potential adjuvants for mucosal delivery of poorly immunogenic vaccines.

Vaccination With a Single Consensus Envelope Protein Ectodomain Sequence Administered in a Heterologous Regimen Induces Tetravalent Immune Responses and Protection Against Dengue Viruses in Mice

“…These intricate interactions during vaccination process might explain why the DDP regimen led to the induction of higher level of antibody and cytokine responses and conferred more effective protection against DENV2 than the DDD or DPP. Taken together, the results suggested that the heterologous DDP immunization regimen would be advantageous in significantly improving the DENV2-specific CD8 + responses and simultaneous Th1 and Th2 responses (Aviles et al, 2015; Wang et al, 2017; Cao et al, 2018; Jung et al, 2018). Therefore, the DDP vaccination regimen would be an appropriate strategy for developing dengue vaccines.…”

Progress in Treatment and Diagnostics of Infectious Disease with Polymers

“…This was not limited to H1N1 but was also used for H3N2 vaccine . The delivery of H5N1 vaccines with cationic polymer such as jetPEI enhanced the immunogenicity and induced antigen specific CD4, CD8 and B cell responses . Polyamidoamine (PAMAM) dendrimers conjugated with 3′- and 6′-sillylactose (3SL and 6SL) were designed and underwent a hemagglutination inhibition assay (HIA, Figure ) with human and avian viruses.…”

“…83 The delivery of H5N1 vaccines with cationic polymer such as jetPEI enhanced the immunogenicity and induced antigen specific CD4, CD8 and B cell responses. 84 Polyamidoamine (PAMAM) dendrimers conjugated with 3′and 6′-sillylactose (3SL and 6SL) were designed and underwent a hemagglutination inhibition assay (HIA, Figure 6) with human and avian viruses. HIA results show that dendrimers conjugated with 6SL inhibit human avian influenza better than those conjugated with 3SL.…”

Enhanced gene transfection efficiency by low-dose 25 kDa polyethylenimine by the assistance of 1.8 kDa polyethylenimine

“…Since first reported in 1995, PEI has been becoming one of the most widely studied gene vehicles characterized with high positive charge density and ‘proton sponge effect’, by which genes can be robustly condensed and protected from endosome or lysozyme capture (Boussif et al., 1995 ; Regnström et al., 2003 ). Transfection reagents such as Gen500, jetPEI, which is developed based on HMW PEIs, are commercially available (Li et al., 2015 ; Cao et al., 2018 ). However, high-gene transfection efficiency always comes along with high cytotoxicity by HMW PEIs (Chollet et al., 2002 ).…”