title: Vectored Gag and Env but not Tat show efficacy against simian-human immunodeficiency virus 89.6P challenge in Mamu-A*01-negative rhesus monkeys.
abstract: Simian-human immunodeficiency virus (SHIV) challenge studies in rhesus macaques were conducted to evaluate the efficacy of adenovirus-based vaccines in the context of different major histocompatibility complex class I genetic backgrounds and different vaccine compositions. Mamu-A*01 allele-negative rhesus monkeys were immunized with one of the following vaccine constructs: (i) replication-defective recombinant adenovirus type 5 (Ad5) expressing human immunodeficiency virus type 1 (HIV-1) Tat (Ad5/HIVTat); (ii) Ad5 vector expressing simian immunodeficiency virus (SIV) Gag (Ad5/SIVGag); (iii) Ad5 vector expressing the truncated HIV-1(jrfl) Env, gp140 (Ad5/gp140_jrfl); (iv) Ad5 vector expressing the SHIV-89.6P gp140 (Ad5/gp140_89.6P); or (v) the combination of Ad5/SIVGag and Ad5/gp140_jrfl. Following intravenous challenge with SHIV-89.6P, only those cohorts that received vaccines expressing Gag or Env exhibited an attenuation of the acute viremia and associated CD4-cell lymphopenia. While no prechallenge neutralizing antibody titers were detectable in either Ad5/gp140-vaccinated group, an accelerated neutralizing antibody response was observed in the Ad5/gp140_89.6P-vaccinated group upon viral challenge. The set-point viral loads in the Ad5/SIVGag- and Ad5/gp140_jrfl-vaccinated groups were associated with the overall strength of the induced cellular immune responses. To examine the contribution of Mamu-A*01 allele in vaccine efficacy against SHIV-89.6P challenge, Mamu-A*01-positive monkeys were immunized with Ad5/SIVGag. Vaccine-mediated protection was significantly more pronounced in the Mamu-A*01-positive monkeys than in Mamu-A*01-negative monkeys, suggesting the strong contributions of T-cell epitopes restricted by the Mamu-A*01 molecule. The implications of these results in the development of an HIV-1 vaccine will be discussed.
authors.affiliation: Merck Research Laboratories, P. O. Box 4, WP16-306, West Point, PA 19486, USA. xiaoping_liang@merck.com
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Fubao
authors.initials: F
authors.lastname: Wang
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Davies
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Tong-Ming
authors.initials: TM
authors.lastname: Fu
authors.forename: Adam C
authors.initials: AC
authors.lastname: Finnefrock
authors.forename: Larry
authors.initials: L
authors.lastname: Handt
authors.forename: Michael P
authors.initials: MP
authors.lastname: Citron
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Heidecker
authors.forename: Aimin
authors.initials: A
authors.lastname: Tang
authors.forename: Minchun
authors.initials: M
authors.lastname: Chen
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wilson
authors.forename: Lori
authors.initials: L
authors.lastname: Gabryelski
authors.forename: Michael
authors.initials: M
authors.lastname: McElhaugh
authors.forename: Anthony
authors.initials: A
authors.lastname: Carella
authors.forename: Cheryl
authors.initials: C
authors.lastname: Moyer
authors.forename: Lingyi
authors.initials: L
authors.lastname: Huang
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vitelli
authors.forename: Deepa
authors.initials: D
authors.lastname: Patel
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007111:Immunity, Cellular; D008253:Macaca mulatta; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014766:Viremia; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D000956:Antigens, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015696:Gene Products, tat; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D018449:SAIDS Vaccines; D054322:tat Gene Products, Human Immunodeficiency Virus