Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease

被引:8
|
作者
Babirye, Peace [1 ]
Musubika, Carol [1 ]
Kirimunda, Samuel [1 ]
Downing, Robert [2 ]
Lutwama, Julian J. [2 ]
Mbidde, Edward K. [2 ]
Weyer, Jacqueline [3 ]
Paweska, Janusz T. [3 ]
Joloba, Moses L. [1 ]
Wayengera, Misaki [1 ,4 ,5 ]
机构
[1] Makerere Univ, Sch Biomed Sci, Dept Immunol & Mol Biol, Coll Hlth Sci, POB 7072, Kampala, Uganda
[2] UVRI, CDC, Arbovirol & Filovirol Labs, Entebbe, Uganda
[3] Natl Inst Communicable Dis, Ctr Emerging Zoonot Dis, Johanesburg, South Africa
[4] Makerere Univ, Coll Hlth Sci, Sch Biomed Sci, Unit Genet & Genom, POB 7072, Kampala, Uganda
[5] Makerere Univ, Coll Hlth Sci, Sch Biomed Sci, Dept Pathol, POB 7072, Kampala, Uganda
来源
BMC INFECTIOUS DISEASES | 2018年 / 18卷
关键词
Ebolavirus; Marburgvirus; Viral hemorrhagic fevers; Rapid diagnostic tests; Glycoprotein; HUMORAL IMMUNE-RESPONSE; PREDICTION; PROTEINS; GULU; GP;
D O I
10.1186/s12879-018-3409-x
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background: Ebolavirus and Marburgvirus are genera of the virus family Filoviridae. Filoviruses cause rare but fatal viral hemorrhagic fevers (VHFs) in remote villages of equatorial Africa with potential for regional and international spread. Point-of-care (POC) rapid diagnostic tests (RDTs) are critical for early epidemic detection, reponse and control. There are 2 RDTs for Zaire ebolavirus (EBOV), but not other Ebolavirus spp. or Marburg marburgvirus (MARV). We validate 3 conserved B cell epitopes of filovirus glycoprotein (GP) using ebola virus diseases (EVD) survivor samples, towards devising pan-filovirus RDTs. Methods: ln-silico Immuno-informatics:- (a) multiple and basic local alignments of amino-acid sequences of filovirus (4 Ebolavirus spp. & MARV) Gp1, 2 and epitope prediction and conservation analyses within context of ClusterW, BLAST-P and the immune epitope database analysis resource (IEDB-AR); alongside (b) in-vitro enzyme immunoassays (EIAs) for SUDV Gp1, 2 antigen and host-specific antibodies (IgM and IgG) among 94 gamma irradiated EVD survivor serum and 9 negative controls. Results: Linear B cell epitopes were present across the entire length of all Gp1, 2, most lying in the region between amino acids positioned 350 and 500. Three seperate epitopes 97/80_GAFFLYDRLAST, 39_YEAGEWAENCY and 500_CGLRQLANETTQALQLFLRATTELR (designated UG-Filo-Peptide- 1, 2 and 3 respectively) were conserved within all studied filovirus species Gp1, 2. Gp1, 2 host specific IgM levels were comparably low (ay. ODs < 0.04 [95% CI: 0.02837 to 0.04033]) among the 9 negative controls and 57 survivor samples analyzed. Host specific IgG levels, on the other hand, were elevated (ay. ODs > 1.7525 [95% CI: 0.3010 to 3.1352]) among the 92 survivor samples relative to the 9 negative controls (ay. ODs <0.2.321 [95% CI: -0.7596 to 0.5372]). Filovirus Gp1, 2 antigen was not detected [ay. ODs < 020] within EVD survivor serum relative to recombinant protein positive controls [ay. ODs = 0.50]. Conclusions: These conserved B cell epitopes of filovirus Gp1, 2 and their derivative antibodies are promising for research and development of RDTs for EVD, with potential for extension to detect MVD.
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页数:19
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