HPV11 mutant virus-like particles elicit immune responses that neutralize virus and delineate a novel neutralizing domain

被引:31
|
作者
Ludmerer, SW
McClements, WL
Wang, XM
Ling, JC
Jansen, KU
Christensen, ND
机构
[1] Merck Res Labs, Dept Parasite Biochem & Cell Biol, Rahway, NJ 07065 USA
[2] Merck Res Labs, Dept Virus & Cell Biol, West Point, PA 19486 USA
[3] Penn State Univ, Milton S Hershey Med Ctr, Dept Pathol, Jake Gittlen Canc Res Inst, Hershey, PA 17033 USA
关键词
D O I
10.1006/viro.1999.0083
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Characterization of the regions of human papillomaviruses (HPVs) that elicit neutralizing immune responses supports studies on viral infectivity and provides insight for the development and evaluation of prophylactic vaccines. HPV11 is a major etiologic agent of genital warts and a likely vaccine candidate. A conformationally dependent epitope for the binding of three neutralizing monoclonal antibodies (mAbs) has been mapped to residues G(131)T(132) of the L1 major capsid protein. The mAbs bind L1 only when it is assembled into virions or into virus-like particles (VLPs) that mimic the capsid structure. We were interested in identifying other domains of L1 that elicit neutralizing responses. To this end, we have generated a panel of mAbs against VLPs derived from HPV11 L1 harboring a G131S substitution. The new mAbs are unlike the neutralizing mAbs previously mapped to residues G(131)T(132) in that they bind both prototype and HPV11:G131S mutant VLPs. Some of the new mAbs neutralized virus in vitro. We have mapped epitopes for three of these new mAbs, as well as a neutralizing mAb generated against HPV11 virions, by measuring binding to HPV6 VLPs substituted with HPV11-like amino acids. Two regions are critical: one defined by HPV11 L1 residues 263-290 and the other by residues 346-349. mAbs H11.H3 and H11.G131S.G3 bind HPV6 VLPs with substitutions derived from the 346-349 region; in addition, H11.G131S.G3 binds HPV6 VLPs with substitutions derived only from the 263-290 region. Although H11.H3 does not bind HPV6 VLPs with substitutions derived from the 263-290 region, binding to HPV6 VLPs is enhanced when both sets of substitutions are present. mAbs H11.G131S.11 and H11.G131S.K5 bind HPV6 VLPs with the 263-290 substitutions, but show little binding to HPV6 VLPs with the 346-349 substitutions. However, binding to HPV6 VLPs is enhanced when substitutions at both regions are present. The 346-349 region has not previously been described as eliciting a neutralizing response for any HPV type. In addition, the work demonstrates a complex binding site contributed by two distinct regions of L1. (C) 2000 Academic Press.
引用
收藏
页码:237 / 245
页数:9
相关论文
共 50 条
  • [1] Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice
    Ming Yang
    Huafang Lai
    Haiyan Sun
    Qiang Chen
    Scientific Reports, 7
  • [2] Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin
    Bright, Rick A.
    Carter, Donald M.
    Daniluk, Shannon
    Toapanta, Franklin R.
    Ahmad, Attiya
    Gavrilov, Victor
    Massare, Mike
    Pushko, Peter
    Mytle, Nutan
    Rowe, Thomas
    Smith, Gale
    Ross, Ted M.
    VACCINE, 2007, 25 (19) : 3871 - 3878
  • [3] Functionalisation of Virus-Like Particles Enhances Antitumour Immune Responses
    Kramer, Katrin
    Al-Barwani, Farah
    Baird, Margaret A.
    Young, Vivienne L.
    Larsen, David S.
    Ward, Vernon K.
    Young, Sarah L.
    JOURNAL OF IMMUNOLOGY RESEARCH, 2019, 2019
  • [4] Immune responses to chemically attached motifs on virus-like particles
    Comellas-Aragones, Marta
    Polonskaya, Zinaida
    Kain, Lisa
    Deng, Shenglou
    Liu, Yang
    Savage, Paul
    Teyton, Luc
    Finn, M. G.
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2012, 243
  • [5] Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein
    Tandavanitj, Rapeepat
    Setthapramote, Chayanee
    De Lorenzo, Giuditta
    Sanchez-Velazquez, Ricardo
    Clark, Jordan J.
    Rocchi, Mara
    Mcinnes, Colin
    Kohl, Alain
    Patel, Arvind H.
    VACCINE, 2024, 42 (09) : 2429 - 2437
  • [6] Virus-like particles: Targeted diagnostic imaging and directed immune responses
    Douglas, Trevor
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 250
  • [7] Western equine encephalitis virus virus-like particles from an insect cell-baculovirus system elicit the strong immune responses in mice
    Ma, JinZhu
    Wang, HuaLei
    Zheng, XueXing
    Wu, HongXia
    Yang, SongTao
    Xia, XianZhu
    BIOTECHNOLOGY JOURNAL, 2021, 16 (08)
  • [8] Hepatitis C virus-like particles combined with novel adjuvant systems enhance virus-specific immune responses
    Qiao, M
    Murata, K
    Davis, AR
    Jeong, SH
    Liang, TJ
    HEPATOLOGY, 2003, 37 (01) : 52 - 59
  • [9] Virus-like particles: Passport to immune recognition
    Grgacic, Elizabeth V. L.
    Anderson, David A.
    METHODS, 2006, 40 (01) : 60 - 65
  • [10] Virus-like particles: innate immune stimulators
    Raghunandan, Ramadevi
    EXPERT REVIEW OF VACCINES, 2011, 10 (04) : 409 - 411