Vectored Gag and Env but not Tat show efficacy against simian-human immunodeficiency virus 89.6P challenge in Mamu-A*01-negative rhesus monkeys.
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.
Liang
Xiaoping
X
Merck Research Laboratories, P. O. Box 4, WP16-306, West Point, PA 19486, USA. xiaoping_liang@merck.com
Casimiro
Danilo R
DR
Schleif
William A
WA
Wang
Fubao
F
Davies
Mary-Ellen
ME
Zhang
Zhi-Qiang
ZQ
Fu
Tong-Ming
TM
Finnefrock
Adam C
AC
Handt
Larry
L
Citron
Michael P
MP
Heidecker
Gwendolyn
G
Tang
Aimin
A
Chen
Minchun
M
Wilson
Keith A
KA
Gabryelski
Lori
L
McElhaugh
Michael
M
Carella
Anthony
A
Moyer
Cheryl
C
Huang
Lingyi
L
Vitelli
Salvatore
S
Patel
Deepa
D
Lin
Jing
J
Emini
Emilio A
EA
Shiver
John W
JW
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
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