PRECLINICAL EFFICACY OF A PROTOTYPE DNA VACCINE - ENHANCED PROTECTION AGAINST ANTIGENIC DRIFT IN INFLUENZA-VIRUS

被引:265
作者
DONNELLY, JJ
FRIEDMAN, A
MARTINEZ, D
MONTGOMERY, DL
SHIVER, JW
MOTZEL, SL
ULMER, JB
LIU, MA
机构
[1] MERCK SHARP & DOHME LTD, DEPT VIRUS & CELL BIOL, RES LABS, West Point, PA 19486 USA
[2] MERCK SHARP & DOHME LTD, DEPT LAB ANIM RESOURCES, RES LABS, West Point, PA 19486 USA
关键词
D O I
10.1038/nm0695-583
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vaccination with plasmid DNA expression vectors encoding foreign proteins elicits antibodies and cell-mediated immunity and protects against disease in animal models. We report a comparison of DNA vaccines, using contemporary human strains of virus, and clinically licensed (inactivated virus or subvirion) vaccines in preclinical animal models, to better predict their efficacy in humans. Influenza DNA vaccines elicited antibodies in both non-human primates and ferrets and protected ferrets against challenge with an antigenically distinct epidemic human influenza virus more effectively than the contemporary clinically licensed vaccine. These studies demonstrate that DNA vaccines may be more effective, particularly against different strains of virus, than inactivated virus or subvirion vaccines.
引用
收藏
页码:583 / 587
页数:5
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共 37 条
[1]  
Chakraverty M., Update: Influenza activity-United States and worldwide, and composition of the 1993-94 influenza vaccine, Morbid. Mortal Weekly Rep, 42, pp. 177-180, (1993)
[2]  
Shu L.L., Bean W.J., Webster R.G., Analysis of the evolution and variation of the human influenza A virus nucleoprotein gene from 1933 to 1990, J. Virol, 67, pp. 2723-2729, (1993)
[3]  
Ito T., Evolutionary analysis of the influenza A virus M gene with comparison of the Ml and M2 proteins, J. Virol, 65, pp. 5491-5498, (1991)
[4]  
Rocha E.P., Comparison of 10 influenza A (H1N1 and H3N2) haemagglutinin sequences obtained directly from clinical specimens to those of MDCK cell- and egg-grown viruses, J. Gen. Virol, 74, pp. 2513-2518, (1993)
[5]  
Nichol K.L., The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community, New Engl. J. Med, 331, pp. 778-784, (1994)
[6]  
Clements M.L., Use of single-gene reassortant viruses to study the role of avian influenza A virus genes in attenuation of wild-type human influenza A virus for squirrel monkeys and adult human volunteers, J. Clin. Microbiol, 30, pp. 655-662, (1992)
[7]  
Murphy B.R., Evaluation of three strains of influenza A virus in humans and in owl, cebus, and squirrel monkeys, Infect. Immun, 28, pp. 688-691, (1980)
[8]  
Berendt R.F., Scott G.H., Evaluation of commercially prepared vaccines for experimentally induced type AJNew JerseyJ76 influenza virus infections in mice and squirrel monkeys, J. Infect Dis., 136, pp. S712-S717, (1977)
[9]  
Berendt R.F., Hall W.C., Reaction of squirrel monkeys to intratracheal inoculation with influenza AJNew JerseyJ76 (Swine) virus, Infect. Immun, 16, pp. 476-479, (1977)
[10]  
Yetter R.A., Barber W.H., Small P.A., Heterotypic immunity to influenza in ferrets, Infect. Immun, 29, pp. 650-653, (1980)