Journal of Experimental Medicine, Vol 169, 1361-1371, Copyright © 1989 by Rockefeller University Press

ARTICLES

Active immunization against virus infections due to antigenic drift by induction of crossreactive cytotoxic T lymphocytes

K Kuwano, M Scott, JF Young and FA Ennis
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.

We have examined whether active immunization with c13 protein, a hybrid protein of the first 81 amino acids of the viral NS1 nonstructural protein and the HA2 subunit of A/PR/8 (H1N1) hemagglutinin, could protect BALB/c mice from challenge with A/PR/8 H1 subtype virus. Mice immunized with the c13 protein had a significant reduction of pulmonary virus titers with A/PR/8 (H1) virus, but failed to limit the replication of A/PC (H3) virus, which reflects the in vitro CTL activity of c13 immune spleen cells. We observed that the epitope recognized by HA2 specific CTL, which are induced by a derivative of c13 protein, is highly conserved among H1 and H2 subtype virus strains. This led us to test whether active immunization with c13 protein would also limit pulmonary virus replication in mice infected with the A/TW virus, a virus of the H1 subtype, which was isolated in 1986, and with a virus of the H2 subtype, A/Japan/305/57. Immunized mice had significantly lower lung virus titers than did control mice, and did not possess any neutralizing antibodies to the challenger viruses. These results indicate that active immunization with a fusion protein containing the cross-reactive CTL epitope protects mice from influenza infection by inducing CTL against influenza A H1 and H2 subtype virus strains, which markedly vary in their antibody binding sites on the HA1. The ability to induce active cross-reactive immunization with a fusion protein which contains a highly conserved CTL epitope offers a model for vaccine approaches against viruses which undergo significant variations in their antibody binding sites.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Charo, J., Lindencrona, J. A., Carlson, L.-M., Hinkula, J., Kiessling, R. (2004). Protective Efficacy of a DNA Influenza Virus Vaccine Is Markedly Increased by the Coadministration of a Schiff Base-Forming Drug. J. Virol. 78: 11321-11326 [Abstract] [Full Text]  
• Jameson, J., Cruz, J., Terajima, M., Ennis, F. A. (1999). Human CD8+ and CD4+ T Lymphocyte Memory to Influenza A Viruses of Swine and Avian Species. J. Immunol. 162: 7578-7583 [Abstract] [Full Text]  
• Jameson, J., Cruz, J., Ennis, F. A. (1998). Human Cytotoxic T-Lymphocyte Repertoire to Influenza A Viruses. J. Virol. 72: 8682-8689 [Abstract] [Full Text]  
• Tamura, M., Kuwano, K., Kurane, I., Ennis, F. A. (1998). Definition of Amino Acid Residues on the Epitope Responsible for Recognition by Influenza A Virus H1-Specific, H2-Specific, and H1- and H2-Cross-Reactive Murine Cytotoxic T-Lymphocyte Clones. J. Virol. 72: 9404-9406 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS