Recombinant influenza virus expressing a fusion protein neutralizing epitope of respiratory syncytial virus (RSV) confers protection without vaccine-enhanced RSV disease

被引:15
作者
Lee, Yu-Na [1 ]
Hwang, Hye Suk [1 ]
Kim, Min-Chul [1 ,2 ]
Lee, Young-Tae [1 ]
Lee, Jong Seok [1 ]
Moore, Martin L. [3 ,4 ]
Kang, Sang-Moo [1 ]
机构
[1] Georgia State Univ, Inst Biomed Sci, Ctr Inflammat Immun & Infect, Atlanta, GA 30303 USA
[2] Anim & Plant Quarantine Agcy, Anyang, Gyeonggi Do, South Korea
[3] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA
[4] Childrens Healthcare Atlanta, Atlanta, GA USA
关键词
Influenza virus; Respiratory syncytial virus; Recombinant; Viral vector; F protein; Neutralizing epitope vaccine; TEMPERATURE-SENSITIVE MUTANT; IMMUNE-RESPONSES; F-GLYCOPROTEIN; BALB/C MICE; ATTACHMENT PROTEIN; LONG-TERM; INFECTION; IMMUNOGENICITY; IMMUNIZATION; REPLICATION;
D O I
10.1016/j.antiviral.2014.12.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Respiratory syncytial virus (RSV) is the leading cause of viral bronchiolitis in both children and the elderly. There is no vaccine available for the prevention of RSV infection. Here, we generated recombinant influenza virus (PR8/RSV.HA-F) expressing an RSV F243-294 neutralizing epitope in the hemagglutinin (HA) as a chimeric protein. Neutralizing antibodies specific for both RSV and influenza virus were induced by a single intranasal immunization of mice with PR8/RSV.HA-F. Mice that were immunized with PR8/RSV.HA-F were protected against RSV infection comparable with live RSV as evidenced by significant reduction of RSV lung viral loads, as well as the absence of lung eosinophilia and RSV-specific cellular immune responses. In contrast, formalin-inactivated RSV-immunized mice showed severe disease and high cellular immune responses in lungs after RSV infection. These findings support a concept that recombinant influenza virus carrying the RSV F243-294 neutralizing epitope can be developed as a promising RSV vaccine candidate which induces protective neutralizing antibodies but avoids lung immunopathology. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 8
页数:8
相关论文
共 46 条
  • [1] CHARACTERIZATION OF 2 ANTIGENIC SITES RECOGNIZED BY NEUTRALIZING MONOCLONAL-ANTIBODIES DIRECTED AGAINST THE FUSION GLYCOPROTEIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS
    ARBIZA, J
    TAYLOR, G
    LOPEZ, JA
    FURZE, J
    WYLD, S
    WHYTE, P
    STOTT, EJ
    WERTZ, G
    SULLENDER, W
    TRUDEL, M
    MELERO, JA
    [J]. JOURNAL OF GENERAL VIROLOGY, 1992, 73 : 2225 - 2234
  • [2] Influenza virus vaccine expressing fusion and attachment protein epitopes of respiratory syncytial virus induces protective antibodies in BALB/c mice
    Bian, Chengrong
    Liu, Shuzhen
    Liu, Na
    Zhang, Guangzhou
    Xing, Li
    Song, Yingwei
    Duan, Yueqiang
    Gu, Hongjing
    Zhou, Ya
    Zhang, Peirui
    Li, Zhiwei
    Zhang, Keming
    Wang, Zhaohai
    Zhang, Shaogeng
    Wang, Xiliang
    Yang, Penghui
    [J]. ANTIVIRAL RESEARCH, 2014, 104 : 110 - 117
  • [3] A recombinant anchorless respiratory syncytial virus (RSV) fusion (F) protein/monophosphoryl lipid A (MPL) vaccine protects against RSV-induced replication and lung pathology
    Blanco, Jorge C. G.
    Boukhvalova, Marina S.
    Pletneva, Lioubov M.
    Shirey, Kari Ann
    Vogel, Stefanie N.
    [J]. VACCINE, 2014, 32 (13) : 1495 - 1500
  • [4] Motavizumab for Prophylaxis of Respiratory Syncytial Virus in High-Risk Children: A Noninferiority Trial
    Carbonell-Estrany, Xavier
    Simoes, Eric A. F.
    Dagan, Ron
    Hall, Caroline B.
    Harris, Brian
    Hultquist, Micki
    Connor, Edward M.
    Losonsky, Genevieve A.
    [J]. PEDIATRICS, 2010, 125 (01) : E35 - E51
  • [5] Overcoming T-cell-mediated immunopathology to achieve safe respiratory syncytial virus vaccination
    Castilow, Elaine M.
    Varga, Steven M.
    [J]. FUTURE VIROLOGY, 2008, 3 (05) : 445 - 454
  • [6] Differential role of gamma interferon in inhibiting pulmonary eosinophilia and exacerbating systemic disease in fusion protein-immunized mice undergoing challenge infection with respiratory syncytial virus
    Castilow, Elaine M.
    Olson, Matthew R.
    Meyerholz, David K.
    Vargal, Steven M.
    [J]. JOURNAL OF VIROLOGY, 2008, 82 (05) : 2196 - 2207
  • [7] An adjuvanted respiratory syncytial virus fusion protein induces protection in aged BALB/c mice
    Cherukuri, Anu
    Stokes, Kate L.
    Patton, Kathryn
    Kuo, Howard
    Sakamoto, Kaori
    Lambert, Stacie
    Stillman, Elizabeth
    Moore, Martin L.
    Lee, Sujin
    [J]. IMMUNITY & AGEING, 2012, 9
  • [8] Influenza virus: Immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza vaccines
    Cox, RJ
    Brokstad, KA
    Ogra, P
    [J]. SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2004, 59 (01) : 1 - 15
  • [9] A COMPARISON IN CHIMPANZEES OF THE IMMUNOGENICITY AND EFFICACY OF LIVE ATTENUATED RESPIRATORY SYNCYTIAL VIRUS (RSV) TEMPERATURE-SENSITIVE MUTANT VACCINES AND VACCINIA VIRUS RECOMBINANTS THAT EXPRESS THE SURFACE GLYCOPROTEINS OF RSV
    CROWE, JE
    COLLINS, PL
    LONDON, WT
    CHANOCK, RM
    MURPHY, BR
    [J]. VACCINE, 1993, 11 (14) : 1395 - 1404
  • [10] A FURTHER ATTENUATED DERIVATIVE OF A COLD-PASSAGED TEMPERATURE-SENSITIVE MUTANT OF HUMAN RESPIRATORY SYNCYTIAL VIRUS RETAINS IMMUNOGENICITY AND PROTECTIVE EFFICACY AGAINST WILD-TYPE CHALLENGE IN SERONEGATIVE CHIMPANZEES
    CROWE, JE
    BUI, PT
    DAVIS, AR
    CHANOCK, RM
    MURPHY, BR
    [J]. VACCINE, 1994, 12 (09) : 783 - 790