title: Comparative analysis of antibody induction and protection against influenza virus infection by DNA immunization with HA, HAe, and HA1 in mice.
abstract: Plasmid DNA vaccines are considered alternatives to inactivated influenza virus vaccines to control influenza. Vaccination with a hemagglutinin (HA)-, HA ectodomain (HAe)-, or HA subunit 1 (HA1)-based vaccine can stimulate protective immunity in animals. The aim of this study was to compare their capacity to induce an antibody response and protection against influenza virus infection in mice after DNA vaccination. We constructed three expression vectors encoding full-length HA, HAe, or HA1 of the A/California/07/2009 influenza A virus and designed three animal experiments: (i) BALB/c mice were immunized twice with 30 μg of the HA, HAe, or HA1 DNA vaccine with high-voltage electroporation (100 V), and 3 weeks after boosting, they were challenged with a lethal dose of virus. (ii) Immunization and challenge were as in experiment i, but with low-voltage electroporation (10 V). (iii) Mice were immunized once with 50 μg of DNA and challenged 1 week later. The immunogenic effects of the three DNA vaccines were evaluated in terms of antibody titer, survival rate, bodyweight change, and lung viral titer. In all three experiments, both HA and HAe induced higher antibody and neutralization titers than HA1. Following challenge with a lethal mouse-adapted homologous virus, both HA and HAe reduced the viral titers in lung washes or offered better protection from weight loss than HA1 in experiments ii and iii. Thus, HA1 induces a lower immune response than HA or HAe when used as a DNA vaccination. Our data should be valuable in choosing the optimal candidate vaccine when faced with the threat of pandemic influenza.
authors.affiliation: Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China, chenjj126@126.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Quanjiao
authors.initials: Q
authors.lastname: Chen
authors.forename: Chaochao
authors.initials: C
authors.lastname: Xiong
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yao
authors.forename: Huadong
authors.initials: H
authors.lastname: Wang
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Wang
authors.forename: Ze
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA