title: Aerosolized adenovirus-vectored vaccine as an alternative vaccine delivery method.
abstract: Conventional parenteral injection of vaccines is limited in its ability to induce locally-produced immune responses in the respiratory tract, and has logistical disadvantages in widespread vaccine administration. Recent studies suggest that intranasal delivery or vaccination in the respiratory tract with recombinant viral vectors can enhance immunogenicity and protection against respiratory diseases such as influenza and tuberculosis, and can offer more broad-based generalized protection by eliciting durable mucosal immune responses. Controlled aerosolization is a method to minimize vaccine particle size and ensure delivery to the lower respiratory tract. Here, we characterize the dynamics of aerosolization and show the effects of vaccine concentration on particle size, vector viability, and the actual delivered dose of an aerosolized adenoviral vector. In addition, we demonstrate that aerosol delivery of a recombinant adenoviral vaccine encoding H1N1 hemagglutinin is immunogenic and protects ferrets against homologous viral challenge. Overall, aerosol delivery offers comparable protection to intramuscular injection, and represents an attractive vaccine delivery method for broad-based immunization campaigns.
authors: Infectious Disease Aerobiology, Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70447, USA.
authors: Chad J
authors: CJ
authors: Roy
authors: Alida
authors: A
authors: Ault
authors: Satheesh K
authors: SK
authors: Sivasubramani
authors: J Patrick
authors: JP
authors: Gorres
authors: Chih-Jen
authors: CJ
authors: Wei
authors: Hanne
authors: H
authors: Andersen
authors: Jason
authors: J
authors: Gall
authors: Mario
authors: M
authors: Roederer
authors: Srinivas S
authors: SS
authors: Rao
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005289:Ferrets; D005822:Genetic Vectors; D057809:HEK293 Cells; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D008297:Male; D009330:Nebulizers and Vaporizers; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010316:Particle Size; D013997:Time Factors; D014162:Transfection; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019562:Viral Load
chemical_list: D000336:Aerosols; D000914:Antibodies, Viral; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic