Induction of CD8 + cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs

• Published in: Nature (London) Vol. 344; no. 6269; pp. 873 - 875
• Main Authors: Takahashi, Hidemi, Takeshfta, Toshiyuki, Morein, Bror, Putney, Scott, Germain, Ronald N, Berzofsky, Jay A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 26.04.1990; Nature Publishing Group
• Subjects: Acquired immune deficiency syndrome; Adjuvants, Immunologic; AIDS; AIDS/HIV; Amino Acid Sequence; Animals; Antigens; Biological and medical sciences; CD4 antigen; CD8 antigen; Contamination; Cytotoxicity; Effector cells; Fibroblasts; Fundamental and applied biological sciences. Psychology; Gene Products, env - immunology; Glycoproteins; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral - immunology; Histocompatibility Antigens Class I - immunology; HIV; HIV Antigens - immunology; HIV Envelope Protein gp160; HIV-1 - immunology; Human immunodeficiency virus; Immunization; Influenza; ISCOMS; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Medical research; Mice; Mice, Inbred BALB C; Microbiology; Molecular Sequence Data; Peptides; Phenotypes; Priming; Protein Precursors - immunology; Proteins; Quillaja Saponins; Risk reduction; Saponins - immunology; Soluble protein antigen; Spleen; T-Lymphocytes, Cytotoxic - immunology; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic; Viral envelope proteins; Virology; Immunization; HIV-1 virus; Hemagglutinin; Induction; Rodentia; Retroviridae; Cytotoxicity; Virus; Proteins; Vertebrata; Mammalia; Mouse; Immunological adjuvant; T-Lymphocyte; Human immunodeficiency virus; Virus envelope
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/344873a0

To reduce the risks of immunization with killed or live attenuated virus vaccines, it may be advantageous to use a pure, defined antigen that contains determinants for both humoral and cellular immunity. However, although most non-living intact protein preparations induce antibodies and CD4+ major histocompatibility complex (MHC) class II-restricted helper and/or cytotoxic T lymphocytes (CTL), they do not elicit CD8+ MHC class I restricted CTL. Indeed, with a few exceptions, it has not so far been possible to induce CD8+ CTL by immunizing with intact soluble proteins. We show here that a single subcutaneous immunization in mice with immunostimulating complexes containing either purified intact gp160 envelope glycoprotein of the human immunodeficiency virus (HIV)-1 or influenza haemagglutinin results in reproducible and long-lasting priming of HIV specific or influenza-specific CD8+, MHC class I restricted CTL.