|Clements,, J. - TULANE UNIV MEDICAL CTR|
|Katz,, Jacqueline - CENTERS FOR DISEASE CTRL|
Submitted to: International Symposium on Avian Influenza
Publication Type: Abstract Only
Publication Acceptance Date: August 5, 2000
Publication Date: September 1, 2000
Technical Abstract: Vaccines that overcome the antigenic variability of influenza A viruses by inducing greater Het-I are desirable. Previously, we demonstrated that intranasal (i.n.) influenza vaccination of mice with an inactivated X-31 (H3N2) vaccine coadministrated with a mutant form of enterotoxin (mLT) from Escherichia coli induced strong Het-I and protected mice against lethal challenge with a highly pathogenic H5N1 influenza A virus subtype. In contrast, mice administered the same dose of X-31 vaccine subcutaneously (s.c) were not protected against lethal H5N1 challenge. The contributions of B cells and CD8 T cells to Het-I were evaluated. Mice that received three i.n. immunizations of X-31 vaccine with mLT developed antiviral serum and lung IgA antibody responses. In contrast, mice vaccinated by the s.c. route failed to develop detectable IgA titers. Splenocytes from mucosal X-31-vaccinated mice also exhibited strong heterosubtypic cytotoxic T lymphocyte (CTL) responses to a heterologous H5N3 virus. We evaluated the functional role of B cells and CD8 T cells in Het-I by using gene-targeted B-cell (IgH-6) or Beta 2-microglobulin (Beta 2m) deficient mice, respectively. It was found that Beta 2m, but not IgH-6 vaccinated mice were protected by Het-I and survived a lethal H5N1 infection with HK/483, suggesting that B cells, but not CD8 T cells are critical for protection of mice against a lethal heterosubtypic challenge.