Anti-respiratory syncytial virus (RSV) G monoclonal antibodies reduce lung inflammation and viral lung titers when delivered therapeutically in a BALB/c mouse model

被引:43
作者
Caidi, Hayat [1 ]
Miao, Congrong [1 ]
Thornburg, Natalie J. [1 ]
Tripp, Ralph A. [2 ]
Anderson, Larry J. [3 ,4 ]
Haynes, Lia M. [1 ]
机构
[1] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Div Viral Dis, Gastroenteritis & Resp Viruses Lab Branch,CDC, Atlanta, GA USA
[2] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA USA
[3] Emory Univ, Div Pediat Infect Dis, Atlanta, GA 30322 USA
[4] Childrens Healthcare Atlanta, Atlanta, GA USA
关键词
RSV; G protein; CX3C; CX3CR1; Virus; Pathogenesis; Monoclonal antibody; G-PROTEIN; G GLYCOPROTEIN; INFECTION; MICE; PROPHYLAXIS; PALIVIZUMAB; PREVENTION; CHALLENGE; RESPONSES; INFANTS;
D O I
10.1016/j.antiviral.2018.04.014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
RSV continues to be a high priority for vaccine and antiviral drug development. Unfortunately, no safe and effective RSV vaccine is available and treatment options are limited. Over the past decade, several studies have focused on the role of RSV G protein on viral entry, viral neutralization, and RSV-mediated pathology. Anti-G murine monoclonal antibody (mAb) 131-2G treatment has been previously shown to reduce weight loss, bronchoalveolar lavage (BAL) cell number, airway reactivity, and Th2-type cytokine production in RSV-infected mice more rapidly than a commercial humanized monoclonal antibody (mAb) against RSV F protein (Palivizumab). In this study, we have tested two human anti-RSV G mAbs, 2B11 and 3D3, by both prophylactic and therapeutic treatment for RSV in the BALB/c mouse model. Both anti-G mAbs reduced viral load, leukocyte infiltration and IFN-gamma and IL-4 expression in cell-free BAL supernatants emphasizing the potential of anti-G mAbs as anti-inflammatory and antiviral strategies.
引用
收藏
页码:149 / 157
页数:9
相关论文
共 45 条
[41]   Antigenic and genetic diversity among the attachment proteins of group a respiratory syncytial viruses that have caused repeat infections in children [J].
Sullender, WM ;
Mufson, MA ;
Prince, GA ;
Anderson, LJ ;
Wertz, GW .
JOURNAL OF INFECTIOUS DISEASES, 1998, 178 (04) :925-932
[42]   CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein [J].
Tripp, RA ;
Jones, LP ;
Haynes, LM ;
Zheng, HQ ;
Murphy, PM ;
Anderson, LJ .
NATURE IMMUNOLOGY, 2001, 2 (08) :732-738
[43]   The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P [J].
Tripp, RA ;
Dakhama, A ;
Jones, LP ;
Barskey, A ;
Gelfand, EW ;
Anderson, LJ .
JOURNAL OF VIROLOGY, 2003, 77 (11) :6580-6584
[44]   Respiratory syncytial virus G and/or SH protein alters Th1 cytokines, natural killer cells, and neutrophils responding to pulmonary infection in BALB/c mice [J].
Tripp, RA ;
Moore, D ;
Jones, L ;
Sullender, W ;
Winter, J ;
Anderson, LJ .
JOURNAL OF VIROLOGY, 1999, 73 (09) :7099-7107
[45]   Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice [J].
Zhang, Wenliang ;
Choi, Youngjoo ;
Haynes, Lia M. ;
Harcourt, Jennifer L. ;
Anderson, Larry J. ;
Jones, Les P. ;
Tripp, Ralph A. .
JOURNAL OF VIROLOGY, 2010, 84 (02) :1148-1157