The failed HIV Merck vaccine study: A step back or a launching point for future vaccine development?

被引：326

作者：

Sekaly, Rafick-Pierre ^{[1
]}

机构：

[1] Univ Montreal, CR CHUM, INSERM, U743, Montreal, PQ H2X 1P1, Canada

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2008年 / 205卷 / 01期

关键词：

D O I：

10.1084/jem.20072681

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The world of human immunodeficiency virus (HIV) vaccines has suffered a baffling setback. The first trial of a vaccine designed to elicit strong cellular immunity has shown no protection against infection. More alarmingly, the vaccine appeared to increase the rate of HIV infection in individuals with prior immunity against the adenovirus vector used in the vaccine. A new study in this issue suggests that a different vaccine approach-using a DNA prime/poxvirus boost strategy-induces polyfunctional immune responses to an HIV immunogen. The disappointing results of the recent vaccine trial suggest that a more thorough assessment of vaccine-induced immune responses is urgently needed, and that more emphasis should be placed on primate models before efficacy trials are undertaken.

引用

页码：7 / 12

页数：6

共 52 条

[11] Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with DNA and recombinant adenoviral vaccine vectors expressing Gag [J].

Casimiro, DR ;

Wang, FB ;

Schleif, WA ;

Liang, XP ;

Zhang, ZQ ;

Tobery, TW ;

Davies, ME ;

McDermott, AB ;

O'Connor, DH ;

Fridman, A ;

Bagchi, A ;

Tussey, LG ;

Bett, AJ ;

Finnefrock, AC ;

Fu, TM ;

Tang, AM ;

Wilson, KA ;

Chen, MC ;

Perry, HC ;

Heidecker, GJ ;

Freed, DC ;

Carella, A ;

Punt, KS ;

Sykes, KJ ;

Huang, LY ;

Ausensi, VI ;

Bachinsky, M ;

Sadasivan-Nair, U ;

Watkins, DI ;

Emini, EA ;

Shiver, JW .

JOURNAL OF VIROLOGY, 2005, 79 (24) :15547-15555

[12] AIDS research - Did Merck's failed HIV vaccine cause harm [J].

Cohen, Jon .

SCIENCE, 2007, 318 (5853) :1048-1049

[13] Aids research - Promising AIDS vaccine's failure leaves field reeling [J].

Cohen, Jon .

SCIENCE, 2007, 318 (5847) :28-29

[14] Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major [J].

Darrah, Patricia A. ;

Patel, Dipti T. ;

De Luca, Paula M. ;

Lindsay, Ross W. B. ;

Davey, Dylan F. ;

Flynn, Barbara J. ;

Hoff, Soren T. ;

Andersen, Peter ;

Reed, Steven G. ;

Morris, Sheldon L. ;

Roederer, Mario ;

Seder, Robert A. .

NATURE MEDICINE, 2007, 13 (07) :843-850

[15] PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression [J].

Day, Cheryl L. ;

Kaufmann, Daniel E. ;

Kiepiela, Photini ;

Brown, Julia A. ;

Moodley, Eshia S. ;

Reddy, Sharon ;

Mackey, Elizabeth W. ;

Miller, Joseph D. ;

Leslie, Alasdair J. ;

DePierres, Chantal ;

Mncube, Zenele ;

Duraiswamy, Jaikumar ;

Zhu, Baogong ;

Eichbaum, Quentin ;

Altfeld, Marcus ;

Wherry, E. John ;

Coovadia, Hoosen M. ;

Goulder, Philip J. R. ;

Klenerman, Paul ;

Ahmed, Rafi ;

Freeman, Gordon J. ;

Walker, Bruce D. .

NATURE, 2006, 443 (7109) :350-354

[16] Developing an AIDS vaccine: Need, uncertainty, hope [J].

Emini, EA ;

Koff, WC .

SCIENCE, 2004, 304 (5679) :1913-1914

[17] Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4 [J].

Gilchrist, M ;

Thorsson, V ;

Li, B ;

Rust, AG ;

Korb, M ;

Kennedy, K ;

Hai, T ;

Bolouri, H ;

Aderem, A .

NATURE, 2006, 441 (7090) :173-178

[18]

Gómez-Román VP, 2006, JAIDS-J ACQ IMM DEF, V43, P270

[19] Functional heterogeneity of memory CD4 T cell responses in different conditions of antigen exposure and persistence [J].

Harari, A ;

Vallelian, F ;

Meylan, PR ;

Pantaleo, G .

JOURNAL OF IMMUNOLOGY, 2005, 174 (02) :1037-1045

[20]

HARARI A, J EXP MED, V205, P63

← 1 2 3 4 5 6 →