Recombinant trimeric HA protein immunogenicity of H5N1 avian influenza viruses and their combined use with inactivated or adenovirus vaccines
Journal
PLoS ONE
Journal Volume
6
Journal Issue
5
Pages
e20052
Date Issued
2011
Author(s)
Abstract
Background: The highly pathogenic avian influenza (HPAI) H5N1 virus continues to cause disease in poultry and humans. The hemagglutinin (HA) envelope protein is the primary target for subunit vaccine development. Methodology/Principal Findings: We used baculovirus-insect cell expression to obtain trimeric recombinant HA (rHA) proteins from two HPAI H5N1 viruses. We investigated trimeric rHA protein immunogenicity in mice via immunizations, and found that the highest levels of neutralizing antibodies resulted from coupling with a PELC/CpG adjuvant. We also found that the combined use of trimeric rHA proteins with (a) an inactivated H5N1 vaccine virus, or (b) a recombinant adenovirus encoding full-length HA sequences for prime-boost immunization, further improved antibody responses against homologous and heterologous H5N1 virus strains. Data from cross-clade prime-boost immunization regimens indicate that sequential immunization with different clade HA antigens increased antibody responses in terms of total IgG level and neutralizing antibody titers. Conclusion/Significance: Our findings suggest that the use of trimeric rHA in prime-boost vaccine regimens represents an alternative strategy for recombinant H5N1 vaccine development. ? 2011 Lin et al.
SDGs
Other Subjects
adenovirus vector; CpG oligodeoxynucleotide; immunoglobulin G; immunoglobulin G1; immunoglobulin G2a; neutralizing antibody; recombinant Influenza virus hemagglutinin; recombinant protein; sorbitan trioleate; squalene; unclassified drug; influenza vaccine; Influenza virus hemagglutinin; Adenovirus; animal experiment; antibody response; antibody titer; article; baculovirus expression system; cladistics; controlled study; female; immunization; immunogenicity; influenza A (H5N1); Influenza virus A H5N1; mouse; nonhuman; nucleotide sequence; treatment outcome; virus inactivation; virus recombinant; virus strain; animal; Bagg albino mouse; enzyme linked immunosorbent assay; immunology; Adenoviridae; Aves; Avian influenza virus; Hexapoda; Mus; Animals; Enzyme-Linked Immunosorbent Assay; Female; Hemagglutinin Glycoproteins, Influenza Virus; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Mice; Mice, Inbred BALB C
Type
journal article