Electroporation of Synthetic DNA Antigens Offers Protection in Nonhuman Primates Challenged with Highly Pathogenic Avian Influenza Virus

被引:107
作者
Laddy, Dominick J. [1 ]
Yan, Jian [1 ]
Khan, Amir S. [3 ]
Andersen, Hanne [2 ]
Cohn, Amanda [2 ]
Greenhouse, Jack [2 ]
Lewis, Mark [2 ]
Manischewitz, Jody [4 ]
King, Lisa R. [4 ]
Golding, Hana [4 ]
Draghia-Akli, Ruxandra [3 ]
Weiner, David B. [1 ]
机构
[1] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[2] Bioqual Inc, Rockville, MD 20850 USA
[3] VGX Pharmaceut Inc, The Woodlands, TX 77381 USA
[4] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA
关键词
A H5N1 VIRUS; LETHAL INFECTION; VACCINE; RESPONSES; MACAQUES; ANTIBODY; IMMUNE; CELLS; STRAIN;
D O I
10.1128/JVI.02335-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Avian influenza highlights the need for novel vaccination techniques that would allow for the rapid design and production of safe and effective vaccines. An ideal platform would be capable of inducing both protective antibodies and potent cellular immune responses. These potential advantages of DNA vaccines remain unrealized due to a lack of efficacy in large animal studies and in human trials. Questions remain regarding the potential utility of cellular immune responses against influenza virus in primates. In this study, by construct optimization and in vivo electroporation of synthetic DNA-encoded antigens, we observed the induction of cross-reactive cellular and humoral immune responses individually capable of providing protection from influenza virus infection in the rhesus macaque. These studies advance the DNA vaccine field and provide a novel, more tolerable vaccine with broad immunogenicity to avian influenza virus. This approach appears important for further investigation, including studies with humans.
引用
收藏
页码:4624 / 4630
页数:7
相关论文
共 30 条
[1]  
BODIESBRAKHOP AM, 2008, EXPERT REV VACCINES, V7, P1085
[2]   CD4 T cell-mediated protection from lethal influenza: Perforin and antibody-mediated mechanisms a one-two punch [J].
Brown, Deborah M. ;
Dilzer, Allison M. ;
Meents, Dana L. ;
Swain, Susan L. .
JOURNAL OF IMMUNOLOGY, 2006, 177 (05) :2888-2898
[3]   Deaths from bacterial pneumonia during 1918-19 influenza pandemic [J].
Brundage, John F. ;
Shanks, G. Dennis .
EMERGING INFECTIOUS DISEASES, 2008, 14 (08) :1193-1199
[4]  
*CDCP, 1997, MMWR-MORBID MORTAL W, V46, P1204
[5]   Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells [J].
Chan, MCW ;
Cheung, CY ;
Chui, WH ;
Tsao, SW ;
Nicholls, JM ;
Chan, YO ;
Chan, RWY ;
Long, HT ;
Poon, LLM ;
Guan, Y ;
Peiris, JSM .
RESPIRATORY RESEARCH, 2005, 6 (1)
[6]   A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses [J].
Chen, Ming-Wei ;
Cheng, Ting-Jen Rachel ;
Huang, Yaoxing ;
Jan, Jia-Tsrong ;
Ma, Shiou-Hwa ;
Yu, Alice L. ;
Wong, Chi-Huey ;
Ho, David D. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (36) :13538-13543
[7]   Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia [J].
de Jong, Menno D. ;
Simmons, Cameron P. ;
Thanh, Tran Tan ;
Hien, Vo Minh ;
Smith, Gavin J. D. ;
Chau, Tran Nguyen Bich ;
Hoang, Dang Minh ;
Chau, Nguyen Van Vinh ;
Khanh, Truong Huu ;
Dong, Vo Cong ;
Qui, Phan Tu ;
Van Cam, Bach ;
Ha, Do Quang ;
Guan, Yi ;
Peiris, J. S. Malik ;
Chinh, Nguyen Tran ;
Hien, Tran Tinh ;
Farrar, Jeremy .
NATURE MEDICINE, 2006, 12 (10) :1203-1207
[8]   A clinical trial of a whole-virus H5N1 vaccine derived from cell culture [J].
Ehrlich, Hartmut J. ;
Mueller, Markus ;
Oh, Helen M. L. ;
Tambyah, Paul A. ;
Joukhadar, Christian ;
Montomoli, Emanuele ;
Fisher, Dale ;
Berezuk, Greg ;
Fritsch, Sandor ;
Loew-Baselli, Alexandra ;
Vartian, Nina ;
Bobrovsky, Roman ;
Pavlova, Borislava G. ;
Poellabauer, Eva Maria ;
Kistner, Otfried ;
Barrett, P. Noel .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (24) :2573-2584
[9]   Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein [J].
Epstein, SL ;
Kong, WP ;
Misplon, JA ;
Lo, CY ;
Tumpey, TM ;
Xu, L ;
Nabel, GJ .
VACCINE, 2005, 23 (46-47) :5404-5410
[10]   Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: An experiment of nature [J].
Epstein, SL .
JOURNAL OF INFECTIOUS DISEASES, 2006, 193 (01) :49-53