Protective efficacy and immunogenicity of an adenoviral vector vaccine encoding the codon-optimized F protein of respiratory syncytial virus.
Adenoviral vectors (AdV) have received considerable attention for vaccine development because of their high immunogenicity and efficacy. In previous studies, it was shown that DNA immunization of mice with codon-optimized expression plasmids encoding the fusion protein of respiratory syncytial virus (RSV F) resulted in enhanced protection against RSV challenge compared to immunization with plasmids carrying the wild-type cDNA sequence of RSV F. In this study, we constructed AdV carrying the codon-optimized full-length RSV F gene (AdV-F) or the soluble form of the RSV F gene (AdV-Fsol). BALB/c mice were immunized twice with AdV-F or AdV-Fsol and challenged with RSV intranasally. Substantial levels of antibody to RSV F were induced by both AdV vaccines, with peak neutralizing-antibody titers of 1:900. Consistently, the viral loads in lung homogenates and bronchoalveolar lavage fluids were significantly reduced by a factor of more than 60,000. The protection against viral challenge could be measured even 8 months after the booster immunization. AdV-F and AdV-Fsol induced similar levels of immunogenicity and protective efficacy. Therefore, these results encourage further development of AdV vaccines against RSV infection in humans.
Department of Molecular and Medical Virology, Ruhr-Universitaet Bochum, Bochum, Germany.
Rebekka
R
Kohlmann
Sarah
S
Schwannecke
Bettina
B
Tippler
Nicola
N
Ternette
Vladimir V
VV
Temchura
Matthias
M
Tenbusch
Klaus
K
Uberla
Thomas
T
Grunwald
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003062:Codon / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D003062:Codon; C526850:F protein, human respiratory syncytial virus; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins