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

• Authors: Weiping Cao, National Center for Immunization and Respiratory Diseases; Margarita Mishina, National Center for Immunization and Respiratory Diseases; Samuel Amoah, National Center for Immunization and Respiratory Diseases; Wadzanai P. Mboko, Purdue University; Caitlin Bohannon, National Center for Immunization and Respiratory Diseases; James McCoy, Emory University; Suresh K. Mittal, Purdue University; Shivaprakash Gangappa, Emory University; Suryaprakash Sambhara, National Center for Immunization and Respiratory Diseases
• Journal Title: Drug Delivery
• Volume: Volume 25, Number 1
• Publisher: Taylor & Francis Open | 2018-03-15, Pages 773-779
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1080/10717544.2018.1450909
• Subjects: Health Sciences, Immunology; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Cationic polymers; H5N1 vaccine; adaptive immunity; protective immunity; mouse model; influenza; HUMAN INFECTION; VIRUS; ADJUVANT; SUBSETS; MICE; POLYETHYLENEIMINE; CHALLENGE; ANTIGENS; MUCOSAL; DESIGN

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.