Antibody-Mediated Protective Mechanisms Induced by a Trivalent Parainfluenza Virus-Vectored Ebolavirus Vaccine.
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Cell Line
Drug Combinations
Ebola Vaccines
/ genetics
Ebolavirus
/ genetics
Epitopes
/ immunology
Female
Ferrets
Genetic Vectors
Glycoproteins
/ immunology
Guinea Pigs
Hemorrhagic Fever, Ebola
/ virology
Parainfluenza Virus 3, Human
/ genetics
Viral Envelope Proteins
/ immunology
Viral Vaccines
/ genetics
Ebola virus
antibody repertoire
immune response
immunization
neutralizing antibodies
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 02 2019
15 02 2019
Historique:
received:
17
10
2018
accepted:
23
11
2018
pubmed:
7
12
2018
medline:
18
12
2019
entrez:
7
12
2018
Statut:
epublish
Résumé
Ebolaviruses Zaire (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) cause human disease with high case fatality rates. Experimental monovalent vaccines, which all utilize the sole envelope glycoprotein (GP), do not protect against heterologous ebolaviruses. Human parainfluenza virus type 3-vectored vaccines offer benefits, including needle-free administration and induction of mucosal responses in the respiratory tract. Multiple approaches were taken to induce broad protection against the three ebolaviruses. While GP consensus-based antigens failed to elicit neutralizing antibodies, polyvalent vaccine immunization induced neutralizing responses to all three ebolaviruses and protected animals from death and disease caused by EBOV, SUDV, and BDBV. As immunization with a cocktail of antigenically related antigens can skew the responses and change the epitope hierarchy, we performed comparative analysis of antibody repertoire and Fc-mediated protective mechanisms in animals immunized with monovalent versus polyvalent vaccines. Compared to sera from guinea pigs receiving the monovalent vaccines, sera from guinea pigs receiving the trivalent vaccine bound and neutralized EBOV and SUDV at equivalent levels and BDBV at only a slightly reduced level. Peptide microarrays revealed a preponderance of binding to amino acids 389 to 403, 397 to 415, and 477 to 493, representing three linear epitopes in the mucin-like domain known to induce a protective antibody response. Competition binding assays with monoclonal antibodies isolated from human ebolavirus infection survivors demonstrated that the immune sera block the binding of antibodies specific for the GP glycan cap, the GP1-GP2 interface, the mucin-like domain, and the membrane-proximal external region. Thus, administration of a cocktail of three ebolavirus vaccines induces a desirable broad antibody response, without skewing of the response toward preferential recognition of a single virus.
Identifiants
pubmed: 30518655
pii: JVI.01845-18
doi: 10.1128/JVI.01845-18
pmc: PMC6364037
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Drug Combinations
0
Ebola Vaccines
0
Epitopes
0
Glycoproteins
0
Viral Envelope Proteins
0
Viral Vaccines
0
envelope glycoprotein, Ebola virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P01 CA174439
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI102887
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109711
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA190158
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
Références
J Exp Med. 2004 Jul 19;200(2):169-79
pubmed: 15249592
Trends Mol Med. 2016 Nov;22(11):969-982
pubmed: 27756530
Virology. 2002 May 25;297(1):136-52
pubmed: 12083844
Am J Trop Med Hyg. 2009 Feb;80(2):302-11
pubmed: 19190230
J Virol. 2015 Oct 14;90(1):266-78
pubmed: 26468533
J Immunol Methods. 2004 Nov;294(1-2):15-22
pubmed: 15604012
Sci Rep. 2016 Feb 10;6:20514
pubmed: 26861827
Cell. 2018 Aug 9;174(4):938-952.e13
pubmed: 30096313
Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17123-7
pubmed: 17942693
J Infect Dis. 1999 Feb;179 Suppl 1:S203-17
pubmed: 9988186
J Infect Dis. 2011 Aug 1;204(3):442-50
pubmed: 21742844
Lancet. 1995 Dec 23-30;346(8991-8992):1669-71
pubmed: 8551825
Int J Exp Pathol. 1995 Aug;76(4):227-36
pubmed: 7547435
Immunity. 2010 Nov 24;33(5):657-70
pubmed: 21094463
Nature. 2014 Oct 2;514(7520):47-53
pubmed: 25171469
Sci Transl Med. 2013 Aug 21;5(199):199ra113
pubmed: 23966302
J Virol. 2006 Mar;80(5):2267-79
pubmed: 16474134
Pediatrics. 1959 Jun;23(6):1041-62
pubmed: 13657588
J Virol. 2002 Dec;76(24):12463-72
pubmed: 12438572
Clin Vaccine Immunol. 2010 Apr;17(4):572-81
pubmed: 20181765
Microbes Infect. 2011 Oct;13(11):930-6
pubmed: 21651988
J Virol. 2015 Oct 21;90(1):392-9
pubmed: 26491156
Nature. 2000 Nov 30;408(6812):605-9
pubmed: 11117750
Virol J. 2012 Jan 25;9:32
pubmed: 22273269
Can Commun Dis Rep. 2016 Jul 07;42(7):149-151
pubmed: 29770021
Pediatr Infect Dis J. 2006 Jan;25(1):12-8
pubmed: 16395096
J Investig Med. 2005 Sep;53(6):292-304
pubmed: 16207466
Viral Immunol. 2015 Feb;28(1):51-61
pubmed: 25494457
Cell. 2016 Jan 28;164(3):392-405
pubmed: 26806128
J Immunol Methods. 2011 Mar 7;366(1-2):8-19
pubmed: 21192942
Immunol Rev. 2007 Oct;219:88-102
pubmed: 17850484
Nat Med. 2014 Oct;20(10):1126-9
pubmed: 25194571
Virology. 2000 Nov 10;277(1):147-55
pubmed: 11062045
J Virol. 2009 Jul;83(14):7296-304
pubmed: 19386702
J Infect Dis. 1999 Feb;179 Suppl 1:S235-9
pubmed: 9988189
PLoS Med. 2006 Jun;3(6):e177
pubmed: 16683867
Vaccine. 2005 Apr 27;23(23):3033-42
pubmed: 15811650
Vaccine. 2011 Apr 5;29(16):3043-54
pubmed: 21320540
J Infect Dis. 2016 Aug 15;214(4):565-9
pubmed: 27354371
Science. 2000 Mar 3;287(5458):1664-6
pubmed: 10698744
J Virol. 2007 Jun;81(12):6379-88
pubmed: 17428868
Nat Med. 2016 Dec;22(12):1439-1447
pubmed: 27798615
Nature. 2008 Jul 10;454(7201):177-82
pubmed: 18615077
Cell Host Microbe. 2018 Aug 8;24(2):221-233.e5
pubmed: 30092199
J Virol. 2002 Jun;76(12):6408-12
pubmed: 12021376
Br Med J. 1963 Jun 15;1(5345):1573-4
pubmed: 13942442
Science. 2015 Jul 3;349(6243):88-91
pubmed: 26138979
J Clin Invest. 2015 Aug 3;125(8):3241-55
pubmed: 26168222
PLoS One. 2014 Jun 10;9(6):e96360
pubmed: 24914933
Proteins. 1993 Sep;17(1):49-61
pubmed: 8234244
Nat Immunol. 2010 Sep;11(9):785-97
pubmed: 20720586
J Virol. 2015 Jan 15;89(2):1314-23
pubmed: 25392221
Nat Med. 2005 Jul;11(7):786-90
pubmed: 15937495
Nat Microbiol. 2018 Jun;3(6):670-677
pubmed: 29736037
Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20690-4
pubmed: 22143789