NEW YORK (Reuters Health) - A vaccine in which Pseudomonas aeruginosa outer membrane protein F (OprF) is fused to an adenoviral capsid protein induces an immune response in mice and protects them from a lethal intrapulmonary challenge with the bacteria, new research shows.
Patients with cystic fibrosis, bronchiectasis and immunodeficiency are prone to infections with P. aeruginosa, making a vaccine against the organism an attractive option, but there is none yet available, Dr. Ronald G. Crystal and colleagues explain in the Journal of Clinical Investigation, published online April 1st.
Using a whole adenovirus vector is ineffective because the host immune response to the virus is so strong that it precludes further infection with the virus and thus prevents boosting with the vaccine.
Dr. Crystal, at Weill Medical College of Cornell University in New York, and colleagues there and at GenVec Inc., in Bethesda, Maryland, decided to use just the adenoviral capsid because it is known to act as an adjuvant and permit boosting. P. aeruginosa epitope 8 of the OprF was inserted into one of the external loops of the vector (AdZ.Epi8).
Mice immunized with the vaccine developed CD4 and CD8 Epi8-specific interferon-gamma responses in spleen cells. IgG antibody responses were generated as well. Repeated immunization with AdZ.Epi8 resulted in expansion of the anti-OprF humoral and cellular responses.
Vaccination with Epi8 alone failed to induce antiOprF IgG titers.
While control mice died within 3 days of a lethal challenge with P. aeruginosa, 80% of mice immunized with AdZ.Epi8 survived for more than 2 weeks.
“The strategy of incorporating epitopes into the Ad capsid, perhaps combined with expression of cDNA encoding the same antigen in the expression cassette, will also be valuable in the development of Ad-based vaccines against other pathogens,” Dr. Crystal’s group suggests.
Source: J Clin Invest 2005. [ Google search on this article ]
MeSH Headings:Capsid: Pseudomonas Infections: Viral Proteins: Virion: CD4-Positive T-Lymphocytes: Viral Structural Proteins: Gram-Negative Bacterial Infections: CD8-Positive T-Lymphocytes: Nucleocapsid: Nucleocapsid ProteinsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
