Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections

被引:95
作者
Swenson, Dana L. [1 ]
Wang, Danher [2 ]
Luo, Min [2 ]
Warfield, Kelly L. [1 ]
Woraratanadharm, Jan [2 ]
Holman, David H. [2 ]
Dong, John Y. [2 ,3 ]
Pratt, William D. [1 ]
机构
[1] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA
[2] GenPhar Inc, Div Biodef Vaccines, Mt Pleasant, SC 29464 USA
[3] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29403 USA
关键词
D O I
10.1128/CVI.00431-07
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack.
引用
收藏
页码:460 / 467
页数:8
相关论文
共 48 条
[1]  
Alibek K., 1999, BIOHAZARD
[2]  
[Anonymous], 2007, Wkly Epidemiol Rec, V82, P345
[3]   Immunization with recombinant adenovirus synthesizing the secretory form of Japanese encephalitis virus envelope protein protects adenovirus-exposed mice against lethal encephalitis [J].
Appaiahgari, MB ;
Saini, M ;
Rauthan, M ;
Jyoti ;
Vrati, S .
MICROBES AND INFECTION, 2006, 8 (01) :92-104
[4]   Ebola outbreak killed 5000 gorillas [J].
Bermejo, Magdalena ;
Rodriguez-Teijeiro, Jose Domingo ;
Illera, German ;
Barroso, Alex ;
Vila, Carles ;
Walsh, Peter D. .
SCIENCE, 2006, 314 (5805) :1564-1564
[5]   A novel adenovirus type 6 (Ad6)-based hepatitis C virus vector that overcomes preexisting anti-Ad5 immunity and induces potent and broad cellular immune responses in rhesus macaques [J].
Capone, S ;
Meola, A ;
Ercole, BB ;
Vitelli, A ;
Pezzanera, M ;
Ruggeri, L ;
Davies, ME ;
Tafi, R ;
Santini, C ;
Luzzago, A ;
Fu, TM ;
Bett, A ;
Colloca, S ;
Cortese, R ;
Nicosia, A ;
Folgori, A .
JOURNAL OF VIROLOGY, 2006, 80 (04) :1688-1699
[6]   Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene [J].
Casimiro, DR ;
Chen, L ;
Fu, TM ;
Evans, RK ;
Caulfield, MJ ;
Davies, ME ;
Tang, A ;
Chen, MC ;
Huang, LY ;
Harris, V ;
Freed, DC ;
Wilson, KA ;
Dubey, S ;
Zhu, DM ;
Nawrocki, D ;
Mach, H ;
Troutman, R ;
Isopi, L ;
Williams, D ;
Hurni, W ;
Xu, Z ;
Smith, JG ;
Wang, S ;
Liu, X ;
Guan, LM ;
Long, R ;
Trigona, W ;
Heidecker, GJ ;
Perry, HC ;
Persaud, N ;
Toner, TJ ;
Su, Q ;
Liang, XP ;
Youil, R ;
Chastain, M ;
Bell, AJ ;
Volkin, DB ;
Emini, EA ;
Shiver, JW .
JOURNAL OF VIROLOGY, 2003, 77 (11) :6305-6313
[7]   Immune responses to adenovirus and adeno-associated virus in humans [J].
Chirmule, N ;
Propert, KJ ;
Magosin, SA ;
Qian, Y ;
Qian, R ;
Wilson, JM .
GENE THERAPY, 1999, 6 (09) :1574-1583
[8]  
Cohen Philip, 2006, IAVI Rep, V10, P1
[9]   Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates:: an efficacy assessment [J].
Daddario-DiCaprio, KM ;
Geisbert, TW ;
Ströher, U ;
Geisbert, JB ;
Grolla, A ;
Fritz, EA ;
Fernando, L ;
Kagan, E ;
Jahrling, PB ;
Hensley, LE ;
Jones, SM ;
Feldmann, H .
LANCET, 2006, 367 (9520) :1399-1404
[10]  
Deng IM, 1978, B WORLD HEALTH ORGAN, V56, P247