title: Impact of vaccination on cytotoxic T lymphocyte immunodominance and cooperation against simian immunodeficiency virus replication in rhesus macaques.
abstract: Cytotoxic T lymphocyte (CTL) responses play a central role in viral suppression in human immunodeficiency virus (HIV) infections. Prophylactic vaccination resulting in effective CTL responses after viral exposure would contribute to HIV control. It is important to know how CTL memory induction by vaccination affects postexposure CTL responses. We previously showed vaccine-based control of a simian immunodeficiency virus (SIV) challenge in a group of Burmese rhesus macaques sharing a major histocompatibility complex class I haplotype. Gag(206-216) and Gag(241-249) epitope-specific CTL responses were responsible for this control. In the present study, we show the impact of individual epitope-specific CTL induction by prophylactic vaccination on postexposure CTL responses. In the acute phase after SIV challenge, dominant Gag(206-216)-specific CTL responses with delayed, naive-derived Gag(241-249)-specific CTL induction were observed in Gag(206-216) epitope-vaccinated animals with prophylactic induction of single Gag(206-216) epitope-specific CTL memory, and vice versa in Gag(241-249) epitope-vaccinated animals with single Gag(241-249) epitope-specific CTL induction. Animals with Gag(206-216)-specific CTL induction by vaccination selected for a Gag(206-216)-specific CTL escape mutation by week 5 and showed significantly less decline of plasma viral loads from week 3 to week 5 than in Gag(241-249) epitope-vaccinated animals without escape mutations. Our results present evidence indicating significant influence of prophylactic vaccination on postexposure CTL immunodominance and cooperation of vaccine antigen-specific and non-vaccine antigen-specific CTL responses, which affects virus control. These findings provide great insights into antigen design for CTL-inducing AIDS vaccines.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
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: Saori
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Teiichiro
authors.initials: T
authors.lastname: Shiino
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Akihiro
authors.initials: A
authors.lastname: Iida
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hara
authors.forename: Tsugumine
authors.initials: T
authors.lastname: Shu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Taeko K
authors.initials: TK
authors.lastname: Naruse
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006678:HIV / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014611:Vaccination; D019562:Viral Load; D014779:Virus Replication
chemical_list: D018984:Epitopes, T-Lymphocyte; D018449:SAIDS Vaccines
references.citation: J Virol. 2008 Feb;82(4):1723-38
references.pmid: 18057253
references.citation: Immunogenetics. 2010 Sep;62(9):601-11
references.pmid: 20640416
references.citation: J Immunol. 2009 Jun 1;182(11):7131-45
references.pmid: 19454710
references.citation: J Virol. 2009 Feb;83(4):1845-55
references.pmid: 19036810
references.citation: J Virol. 2001 Dec;75(23):11891-6
references.pmid: 11689672
references.citation: Nat Med. 2007 Jan;13(1):46-53
references.pmid: 17173051
references.citation: J Virol. 2009 Sep;83(18):9339-46
references.pmid: 19587045
references.citation: J Infect Dis. 1997 Aug;176(2):362-73
references.pmid: 9237701
references.citation: J Virol. 2006 Jun;80(12):5875-85
references.pmid: 16731926
references.citation: Nat Med. 1996 Apr;2(4):405-11
references.pmid: 8597949
references.citation: J Virol. 2010 Oct;84(19):9879-88
references.pmid: 20660184
references.citation: J Virol. 2009 Aug;83(15):7641-8
references.pmid: 19458000
references.citation: J Virol. 2006 May;80(10):5074-7
references.pmid: 16641299
references.citation: AIDS. 2003 Dec 5;17(18):2581-91
references.pmid: 14685052
references.citation: J Virol. 1994 Sep;68(9):6103-10
references.pmid: 8057491
references.citation: J Virol. 2006 Feb;80(4):1949-58
references.pmid: 16439550
references.citation: J Virol. 1998 Jan;72(1):164-9
references.pmid: 9420212
references.citation: J Virol. 2008 Oct;82(20):10199-206
references.pmid: 18667518
references.citation: J Virol. 2009 Mar;83(6):2743-55
references.pmid: 19116253
references.citation: Nat Med. 2009 Mar;15(3):293-9
references.pmid: 19219024
references.citation: J Virol. 2010 Jun;84(11):5540-9
references.pmid: 20335261
references.citation: Nature. 2009 Jan 1;457(7225):87-91
references.pmid: 18997770
references.citation: J Virol. 2011 Sep;85(18):9334-45
references.pmid: 21752903
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2709-14
references.pmid: 10694578
references.citation: J Immunol. 2011 Jun 15;186(12):6914-24
references.pmid: 21576505
references.citation: Science. 1999 Feb 5;283(5403):857-60
references.pmid: 9933172
references.citation: J Exp Med. 2004 Jun 21;199(12):1709-18
references.pmid: 15210746
references.citation: J Virol. 2002 Aug;76(16):8276-84
references.pmid: 12134033
references.citation: J Virol. 2003 Feb;77(4):2736-40
references.pmid: 12552014
references.citation: Nat Rev Immunol. 2004 Aug;4(8):630-40
references.pmid: 15286729
references.citation: Cell. 1991 May 17;65(4):651-62
references.pmid: 2032289
references.citation: Nat Rev Immunol. 2008 Aug;8(8):619-30
references.pmid: 18617886
references.citation: Science. 2006 Jun 9;312(5779):1530-3
references.pmid: 16763152
references.citation: PLoS One. 2011;6(6):e20479
references.pmid: 21695251
references.citation: J Virol. 1994 Jul;68(7):4650-5
references.pmid: 8207839
references.citation: PLoS One. 2011 Jan 20;6(1):e15639
references.pmid: 21283794