Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes.
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.
Miller
M D
MD
New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772.
Gould-Fogerite
S
S
Shen
L
L
Woods
R M
RM
Koenig
S
S
Mannino
R J
RJ
Letvin
N L
NL
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D002460:Cell Line; D015683:Gene Products, gag / Q000276:immunology*; D005805:Genes, MHC Class I; D008081:Liposomes; D008253:Macaca mulatta; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D011510:Proteolipids / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D016827:CD8 Antigens; D015683:Gene Products, gag; D008081:Liposomes; D011510:Proteolipids; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C020485:proteoliposomes