Development of bioluminescence imaging of respiratory syncytial virus (RSV) in virus-infected live mice and its use for evaluation of therapeutics and vaccines

被引：13
作者：
Fuentes, Sandra [1 ]
Arenas, Diego [1 ]
Moore, Martin M. [2 ]
Golding, Hana [1 ]
Khurana, Surender [1 ]
机构：
[1] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA
[2] Emory Univ, Emory Childrens Ctr Childhood Infect & Vaccines, Sch Med, Emory Childrens Ctr, Atlanta, GA 30322 USA
来源：
VACCINE | 2017年 / 35卷 / 04期
关键词：
RSV; Vaccine; Neutralization; Antibody; Palivizumab; Live imaging. Ds-Cav1; F protein; Pre-fusion F; Animal model; Immune complex; Efficacy; Therapeutic; Treatment; HUMANIZED MONOCLONAL-ANTIBODY; BRONCHOPULMONARY DYSPLASIA; NEUTRALIZING ANTIBODY; PREMATURE-INFANTS; T-CELLS; SAFETY; PHARMACOKINETICS; PROTEIN; CHALLENGE; CHILDREN;
D O I：
10.1016/j.vaccine.2016.11.044
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Respiratory Syncytial virus (RSV) is one of the leading causes of pneumonia among infants with no human vaccine or efficient curative treatments. Efforts are underway to develop new RSV vaccines and therapeutics. There is a dire need for animal models for preclinical evaluation and selection of products against RSV. Herein, we developed a whole body bioluminescence imaging to follow replication of RSV A2 virus strain expressing firefly luciferase (RSVA2-linel9-FFL) in live BALB/c mice that can be used as an extremely sensitive readout for studying effects of antiviral and vaccines in living mice. Strong bioluminescence signal was detected in the nasal cavity and in the lungs following intranasal infection of mice with RSVA2-linel9-FFL. The kinetics of viral replication in lungs quantified by daily live imaging strongly correlated with viral titers measured by ex-vivo plaque assay and by assessing viral RNA by qRT-PCR. Vaccination of mice with a pre-fusion F protein elicited high neutralizing antibody titers conferring strong protective immunity against virus replication in the nasal cavity and lungs. In contrast, post challenge treatment of mice with the monoclonal antibody Palivizumab two days after infection reduced viral replication in the nasal cavity at day 4, but only modestly reduced virus loads in the lungs by day 5. In contrast to RSV bioluminescence, plaque assay did not detect viral titers in lungs on day 5 in Palivizumab-treated animals. This difference between viral loads measured by the two assays was found to be due to coating of virions with the Palivizumab that blocked infection of target cells in vitro and shows importance of live imaging in evaluation of RSV therapeutics. This recombinant RSV based live imaging animal model is convenient and valuable tool that can be used to study host dissemination of RSV and evaluation of antiviral compounds and vaccines against RSV. Published by Elsevier Ltd.
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页码：694 / 702
页数：9
相关论文
共 22 条
[1]   Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease [J].
Feltes, TF ;
Cabalka, AK ;
Meissner, C ;
Piazza, FM ;
Carlin, DA ;
Top, FH ;
Connor, EM ;
Sondheimer, HM .
JOURNAL OF PEDIATRICS, 2003, 143 (04) :532-540
[2]   Nonglycosylated G-Protein Vaccine Protects against Homologous and Heterologous Respiratory Syncytial Virus (RSV) Challenge, while Glycosylated G Enhances RSV Lung Pathology and Cytokine Levels [J].
Fuentes, Sandra ;
Coyle, Elizabeth M. ;
Golding, Hana ;
Khurana, Surender .
JOURNAL OF VIROLOGY, 2015, 89 (16) :8193-8205
[3]   Development of a simple, rapid, sensitive, high-throughput luciferase reporter based microneutralization test for measurement of virus neutralizing antibodies following Respiratory Syncytial Virus vaccination and infection [J].
Fuentes, Sandra ;
Crim, Roberta L. ;
Beeler, Judy ;
Teng, Michael N. ;
Golding, Hana ;
Khurana, Surender .
VACCINE, 2013, 31 (37) :3987-3994
[4]   Safety procedures of coagulation factors [J].
Jorquera, J. I. .
HAEMOPHILIA, 2007, 13 :41-46
[5]   RESPIRATORY SYNCYTIAL VIRUS DISEASE IN INFANTS DESPITE PRIOR ADMINISTRATION OF ANTIGENIC INACTIVATED VACCINE [J].
KIM, HW ;
CANCHOLA, JG ;
BRANDT, CD ;
PYLES, G ;
CHANOCK, RM ;
JENSEN, K ;
PARROTT, RH .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 1969, 89 (04) :422-+
[6]   Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus [J].
McLellan, Jason S. ;
Chen, Man ;
Joyce, M. Gordon ;
Sastry, Mallika ;
Stewart-Jones, Guillaume B. E. ;
Yang, Yongping ;
Zhang, Baoshan ;
Chen, Lei ;
Srivatsan, Sanjay ;
Zheng, Anqi ;
Zhou, Tongqing ;
Graepel, Kevin W. ;
Kumar, Azad ;
Moin, Syed ;
Boyington, Jeffrey C. ;
Chuang, Gwo-Yu ;
Soto, Cinque ;
Baxa, Ulrich ;
Bakker, Arjen Q. ;
Spits, Hergen ;
Beaumont, Tim ;
Zheng, Zizheng ;
Xia, Ningshao ;
Ko, Sung-Youl ;
Todd, John-Paul ;
Rao, Srinivas ;
Graham, Barney S. ;
Kwong, Peter D. .
SCIENCE, 2013, 342 (6158) :592-598
[7]   Structure of RSV Fusion Glycoprotein Trimer Bound to a Prefusion-Specific Neutralizing Antibody [J].
McLellan, Jason S. ;
Chen, Man ;
Leung, Sherman ;
Graepel, Kevin W. ;
Du, Xiulian ;
Yang, Yongping ;
Zhou, Tongqing ;
Baxa, Ulrich ;
Yasuda, Etsuko ;
Beaumont, Tim ;
Kumar, Azad ;
Modjarrad, Kayvon ;
Zheng, Zizheng ;
Zhao, Min ;
Xia, Ningshao ;
Kwong, Peter D. ;
Graham, Barney S. .
SCIENCE, 2013, 340 (6136) :1113-1117
[8]   Comparative effects of two neutralizing anti-respiratory syncytial virus (RSV) monoclonal antibodies in the RSV murine model:: Time versus potency [J].
Mejías, A ;
Chávez-Bueno, S ;
Ríos, AM ;
Aten, MF ;
Raynor, B ;
Peromingo, E ;
Soni, P ;
Olsen, KD ;
Kiener, PA ;
Gómez, AM ;
Jafri, HS ;
Ramilo, O .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (11) :4700-4707
[9]   Anti-respiratory syncytial virus (RSV) neutralizing antibody decreases lung inflammation, airway obstruction, and airway hyerresponsiveness in a murine RSV model [J].
Mejías, A ;
Cádvez-Bueno, S ;
Ríos, AM ;
Saavedra-Lozano, J ;
Aten, MF ;
Hatfield, J ;
Kapur, P ;
Gómez, AM ;
Jafri, HS ;
Ramilo, O .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (05) :1811-1822
[10]   A Chimeric A2 Strain of Respiratory Syncytial Virus (RSV) with the Fusion Protein of RSV Strain Line 19 Exhibits Enhanced Viral Load, Mucus, and Airway Dysfunction [J].
Moore, Martin L. ;
Chi, Michael H. ;
Luongo, Cindy ;
Lukacs, Nicholas W. ;
Polosukhin, Vasiliy V. ;
Huckabee, Matthew M. ;
Newcomb, Dawn C. ;
Buchholz, Ursula J. ;
Crowe, James E., Jr. ;
Goleniewska, Kasia ;
Williams, John V. ;
Collins, Peter L. ;
Peebles, R. Stokes, Jr. .
JOURNAL OF VIROLOGY, 2009, 83 (09) :4185-4194
123