Journal of Experimental Medicine, Vol 176, 1739-1744, Copyright © 1992 by Rockefeller University Press

ARTICLES

Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes

MD Miller, S Gould-Fogerite, L Shen, RM Woods, S Koenig, RJ Mannino and NL Letvin
New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772.

An effective vaccine against the human immunodeficiency virus should be capable of eliciting both an antibody and a cytotoxic T lymphocyte (CTL) response. However, when viral proteins and peptides are formulated with traditional immunological adjuvants and inoculated via a route acceptable for use in humans, they have not been successful at eliciting virus-specific, major histocompatibility complex (MHC) class I-restricted CTL. We have designed a novel viral subunit vaccine by encapsulating a previously defined synthetic peptide CTL epitope of the simian immunodeficiency virus (SIV) gag protein within a proteoliposome capable of attaching to and fusing with plasma membranes. Upon fusing, the encapsulated contents of this proteoliposome can enter the MHC class I processing pathway through the cytoplasm. In this report, we show that after a single intramuscular vaccination, rhesus monkeys develop a CD8+ cell-mediated, MHC class I-restricted CTL response that recognizes the synthetic peptide immunogen. The induced CTL also demonstrate antiviral immunity by recognizing SIV gag protein endogenously processed by target cells infected with SIV/vaccinia recombinant virus. These results demonstrate that virus-specific, MHC class I-restricted, CD8+ CTL can be elicited by a safe, nonreplicating viral subunit vaccine in a primate model for acquired immune deficiency syndrome. Moreover, the proteoliposome vaccine formation described can include multiple synthetic peptide epitopes, and, thus, offers a simple means of generating antiviral cell-mediated immunity in a genetically heterogeneous population.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Kunisawa, J., Nakanishi, T., Takahashi, I., Okudaira, A., Tsutsumi, Y., Katayama, K., Nakagawa, S., Kiyono, H., Mayumi, T. (2001). Sendai Virus Fusion Protein-Mediates Simultaneous Induction of MHC Class I/II-Dependent Mucosal and Systemic Immune Responses Via the Nasopharyngeal-Associated Lymphoreticular Tissue Immune System. J. Immunol. 167: 1406-1412 [Abstract] [Full Text]  
• Egan, M. A., Charini, W. A., Kuroda, M. J., Schmitz, J. E., Racz, P., Tenner-Racz, K., Manson, K., Wyand, M., Lifton, M. A., Nickerson, C. E., Fu, T., Shiver, J. W., Letvin, N. L. (2000). Simian Immunodeficiency Virus (SIV) gag DNA-Vaccinated Rhesus Monkeys Develop Secondary Cytotoxic T-Lymphocyte Responses and Control Viral Replication after Pathogenic SIV Infection. J. Virol. 74: 7485-7495 [Abstract] [Full Text]  
• Wang, R., Doolan, D. L., Charoenvit, Y., Hedstrom, R. C., Gardner, M. J., Hobart, P., Tine, J., Sedegah, M., Fallarme, V., Sacci, J. B. Jr., Kaur, M., Klinman, D. M., Hoffman, S. L., Weiss, W. R. (1998). Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids. Infect. Immun. 66: 4193-4202 [Abstract] [Full Text]  
• Allen, T. M., Sidney, J., del Guercio, M.-F., Glickman, R. L., Lensmeyer, G. L., Wiebe, D. A., DeMars, R., Pauza, C. D., Johnson, R. P., Sette, A., Watkins, D. I. (1998). Characterization of the Peptide Binding Motif of a Rhesus MHC Class I Molecule (Mamu-A*01) That Binds an Immunodominant CTL Epitope from Simian Immunodeficiency Virus. J. Immunol. 160: 6062-6071 [Abstract] [Full Text]  
• Richards, R. L., Rao, M., Wassef, N. M., Glenn, G. M., Rothwell, S. W., Alving, C. R. (1998). Liposomes Containing Lipid A Serve as an Adjuvant for Induction of Antibody and Cytotoxic T-Cell Responses against RTS,S Malaria Antigen. Infect. Immun. 66: 2859-2865 [Abstract] [Full Text]  
• Kuroda, M. J., Schmitz, J. E., Barouch, D. H., Craiu, A., Allen, T. M., Sette, A., Watkins, D. I., Forman, M. A., Letvin, N. L. (1998). Analysis of Gag-specific Cytotoxic T Lymphocytes in Simian Immunodeficiency Virus-infected Rhesus Monkeys by Cell Staining with a Tetrameric Major Histocompatibility Complex Class I-Peptide Complex. JEM 187: 1373-1381 [Abstract] [Full Text]  
• Rabinovich, N., McInnes, P, Klein, D., Hall, B. (1994). Vaccine technologies: view to the future. Science 265: 1401-1404 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS