Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

被引:47
作者
Abbink, Peter [1 ]
Maxfield, Lori F. [1 ]
Ng'ang'a, David [1 ]
Borducchi, Erica N. [1 ]
Iampietro, M. Justin [1 ]
Bricault, Christine A. [1 ]
Teigler, Jeffrey E. [1 ]
Blackmore, Stephen [1 ]
Parenteau, Lily [1 ]
Wagh, Kshitij [3 ,4 ]
Handley, Scott A. [5 ]
Zhao, Guoyan [5 ]
Virgin, Herbert W. [5 ]
Korber, Bette [3 ,4 ]
Barouch, Dan H. [1 ,2 ]
机构
[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA
[2] Ragon Inst MGH MIT & Harvard, Boston, MA USA
[3] Los Alamos Natl Lab, Los Alamos, NM USA
[4] New Mexico Consortium, Los Alamos, NM USA
[5] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
关键词
HIV-1 ENV VACCINE; NEUTRALIZING ANTIBODIES; CHIMPANZEE ADENOVIRUS; CYTOKINE RESPONSES; VIRUS; GENE; IMMUNOGENICITY; CHALLENGES; EFFICACY; CELLS;
D O I
10.1128/JVI.02950-14
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. IMPORTANCE Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens.
引用
收藏
页码:1512 / 1522
页数:11
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