title: Gag-specific cytotoxic T-lymphocyte-based control of primary simian immunodeficiency virus replication in a vaccine trial.
abstract: Gag-specific cytotoxic T lymphocytes (CTLs) exert strong suppressive pressure on human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. However, it has remained unclear whether they can actually contain primary viral replication. Recent trials of prophylactic vaccines inducing virus-specific T-cell responses have indicated their potential to confer resistance against primary SIV replication in rhesus macaques, while the immunological determinant for this vaccine-based viral control has not been elucidated thus far. Here we present evidence implicating Gag-specific CTLs as responsible for the vaccine-based primary SIV control. Prophylactic vaccination using a Gag-expressing Sendai virus vector resulted in containment of SIVmac239 challenge in all rhesus macaques possessing the major histocompatibility complex (MHC) haplotype 90-120-Ia. In contrast, 90-120-Ia-positive vaccinees failed to contain SIVs carrying multiple gag CTL escape mutations that had been selected, at the cost of viral fitness, in SIVmac239-infected 90-120-Ia-positive macaques. These results show that Gag-specific CTL responses do play a crucial role in the control of wild-type SIVmac239 replication in vaccinees. This study implies the possibility of Gag-specific CTL-based primary HIV containment by prophylactic vaccination, although it also suggests that CTL-based AIDS vaccine efficacy may be abrogated in viral transmission between MHC-matched individuals.
authors.affiliation: International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kawada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Nami
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kurihara
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Chikaya
authors.initials: C
authors.lastname: Moriya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Akari
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D000818:Animals; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D017354:Point Mutation; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D015683:Gene Products, gag; D018449:SAIDS Vaccines