Pulmonary delivery of respiratory syncytial virus DNA vaccines using macroaggregated albumin particles.
At present there is no safe and effective vaccine for respiratory syncytial virus (RSV). DNA vaccines encoding RSV surface glycoproteins are one option being examined. Current methods to deliver DNA vaccines generally require repeated high dose intramuscular or intradermal administration for effectiveness. In this study, we examine the efficacy of pulmonary DNA vaccination using low dose DNA vaccines encoding the RSV F glycoprotein conjugated to macroaggregated albumin (MAA-F). Single vaccination of BALB/c mice with 1 microg MAA-F was ineffective, however mice boosted with an additional 1 microg MAA-F, or vaccinated a single time with 10 microg MAA-F, developed substantially improved immunity associated with reduced viral titers, increased anti-F antibody responses, and enhanced Th1 and Th2 intracellular cytokine responses. This study shows that MAA may be a useful carrier for RSV DNA vaccines.
Harcourt
Jennifer L
JL
Respiratory and Enteric Viruses Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, National Center for Infectious Diseases, 1600 Clifton Road NE, Mailstop G-09, Atlanta, GA 30333, USA.
Anderson
Larry J
LJ
Sullender
Wayne
W
Tripp
Ralph A
RA
D000281:Administration, Intranasal; D000418:Albumins; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017252:CD3 Complex / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D005260:Female; D007962:Leukocytes; D008168:Lung / Q000473:pathology / Q000821:virology; D016131:Lymphocyte Subsets; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology
D000418:Albumins; D000914:Antibodies, Viral; D017252:CD3 Complex; D016207:Cytokines; D022261:Respiratory Syncytial Virus Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins