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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.
Highlights
Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds and cause no illness in most cases
In 2007, a non-adjuvanted subvirion H5N1 avian influenza vaccine was approved by US Food and Drug Administration (FDA), but it requires two doses of 90 lg of hemagglutinin (HA), as compared to 15 lg of HA used for seasonal influenza vaccine
We examined the memory Bcell response in the spleen upon booster immunization by measuring the frequency of H5N1-specific antibody-secreting cells (ASCs) by an ELISPOT assay
Summary
Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds and cause no illness in most cases. H7N2, H7N9, H10N8, H6N1 and H5N6 viruses have crossed the species barrier to cause human infections (Gao et al, 2013; Shi et al, 2013; Zhang et al, 2014; Yang et al, 2015). In 2007, a non-adjuvanted subvirion H5N1 avian influenza vaccine was approved by US Food and Drug Administration (FDA), but it requires two doses of 90 lg of hemagglutinin (HA), as compared to 15 lg of HA used for seasonal influenza vaccine. The continuing challenges including viral antigenic drift and shift, the high-dose vaccine requirement, the limited vaccine manufacturing capacity, and non-availability of proprietary adjuvants warrant developing novel formulations, adjuvants, and alternative delivery systems to improve the immunogenicity and protective efficacy of avian influenza vaccines
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