Open AccessVectored Gag and Env but Not Tat Show Efficacy against Simian-Human Immunodeficiency Virus 89.6P Challenge in Mamu-A * 01-Negative Rhesus Monkeys
Author(s) -
Xiaoping Liang,
Danilo R. Casimiro,
William A. Schleif,
Fubao Wang,
MaryEllen Davies,
Zhiqiang Zhang,
Tong-Ming Fu,
Adam C. Finnefrock,
Larry Handt,
Michael Citron,
Gwendolyn J. Heidecker,
Aimin Tang,
Minchun Chen,
Keith A. Wilson,
Lori J. Gabryelski,
Michael McElhaugh,
Anthony Carella,
Cheryl A. Moyer,
Lingyi Huang,
Salvatore Vitelli,
Deepa Patel,
Jianhua Lin,
Emilio A. Emini,
John W. Shiver
Publication year - 2005
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.79.19.12321-12331.2005
Subject(s) - virology , simian immunodeficiency virus , biology , viremia , neutralizing antibody , viral vector , virus , antibody , aids vaccines , vector (molecular biology) , viral load , context (archaeology) , immunology , immune system , recombinant dna , vaccination , gene , genetics , paleontology , vaccine trial
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.