Comparison of adjuvants to optimize influenza neutralizing antibody responses.
AF03
Adjuvants
Influenza vaccine
Nanoparticles
STING agonists
TLR agonists
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
30 09 2019
30 09 2019
Historique:
received:
01
04
2019
revised:
26
07
2019
accepted:
17
08
2019
pubmed:
9
9
2019
medline:
22
9
2020
entrez:
9
9
2019
Statut:
ppublish
Résumé
Seasonal influenza vaccines represent a positive intervention to limit the spread of the virus and protect public health. Yet continual influenza evolution and its ability to evade immunity pose a constant threat. For these reasons, vaccines with improved potency and breadth of protection remain an important need. We previously developed a next-generation influenza vaccine that displays the trimeric influenza hemagglutinin (HA) on a ferritin nanoparticle (NP) to optimize its presentation. Similar to other vaccines, HA-nanoparticle vaccine efficacy is increased by the inclusion of adjuvants during immunization. To identify the optimal adjuvants to enhance influenza immunity, we systematically analyzed TLR agonists for their ability to elicit immune responses. HA-NPs were compatible with nearly all adjuvants tested, including TLR2, TLR4, TLR7/8, and TLR9 agonists, squalene oil-in-water mixtures, and STING agonists. In addition, we chemically conjugated TLR7/8 and TLR9 ligands directly to the HA-ferritin nanoparticle. These TLR agonist-conjugated nanoparticles induced stronger antibody responses than nanoparticles alone, which allowed the use of a 5000-fold-lower dose of adjuvant than traditional admixtures. One candidate, the oil-in-water adjuvant AF03, was also tested in non-human primates and showed strong induction of neutralizing responses against both matched and heterologous H1N1 viruses. These data suggest that AF03, along with certain TLR agonists, enhance strong neutralizing antibody responses following influenza vaccination and may improve the breadth, potency, and ultimately vaccine protection in humans.
Identifiants
pubmed: 31493950
pii: S0264-410X(19)31094-1
doi: 10.1016/j.vaccine.2019.08.030
pmc: PMC6771022
mid: NIHMS1539152
pii:
doi:
Substances chimiques
Adjuvants, Immunologic
0
Antibodies, Neutralizing
0
Hemagglutinins
0
Influenza Vaccines
0
Toll-Like Receptors
0
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6208-6220Subventions
Organisme : Intramural NIH HHS
ID : ZIA AI005003-17
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
Références
J Immunol. 2013 Apr 15;190(8):4103-15
pubmed: 23509365
PLoS One. 2013;8(3):e60038
pubmed: 23555875
Science. 2009 Jul 10;325(5937):197-201
pubmed: 19465683
Immunotherapy. 2009 Nov;1(6):949-64
pubmed: 20563267
Sci Transl Med. 2015 Apr 15;7(283):283ra52
pubmed: 25877890
Colloids Surf B Biointerfaces. 2014 Jan 1;113:312-9
pubmed: 24121074
Cell Rep. 2015 May 19;11(7):1018-30
pubmed: 25959818
Bioconjug Chem. 2016 Oct 19;27(10):2372-2385
pubmed: 27583777
BMC Infect Dis. 2017 Jan 5;17(1):19
pubmed: 28056837
MMWR Morb Mortal Wkly Rep. 2018 Jan 26;67(3):103-108
pubmed: 29370152
Curr Opin Virol. 2016 Apr;17:95-103
pubmed: 26927813
Skin Therapy Lett. 2012 Apr;17(4):5-7
pubmed: 22491804
J Virol. 2014 Apr;88(8):4047-57
pubmed: 24501410
MMWR Morb Mortal Wkly Rep. 2018 Apr 20;67(15):455-458
pubmed: 29672472
Int J Pharm. 2015;486(1-2):99-111
pubmed: 25794609
Vaccine. 2006 Nov 30;24(49-50):7167-74
pubmed: 16884836
Med Sci (Basel). 2017 Dec 18;5(4):
pubmed: 29258267
Adv Drug Deliv Rev. 2009 Mar 28;61(3):248-55
pubmed: 19272313
Expert Rev Vaccines. 2013 Jul;12(7):809-19
pubmed: 23885825
Front Immunol. 2016 Jul 29;7:284
pubmed: 27524984
Expert Rev Vaccines. 2017 Jan;16(1):55-63
pubmed: 27448771
Curr Opin Immunol. 2017 Aug;47:44-51
pubmed: 28734174
Annu Rev Immunol. 2002;20:709-60
pubmed: 11861616
Immune Netw. 2017 Oct;17(5):326-342
pubmed: 29093654
J Control Release. 2018 Jan 28;270:1-13
pubmed: 29170142
Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15987-91
pubmed: 17043214
Vaccine. 2017 Oct 27;35(45):6137-6142
pubmed: 28967521
Expert Rev Vaccines. 2012 Jun;11(6):645-57
pubmed: 22873123
Eur J Immunol. 2005 Jan;35(1):282-9
pubmed: 15580661
Vaccine. 2014 Jan 9;32(3):327-37
pubmed: 24295808
Int Immunol. 2001 Jul;13(7):933-40
pubmed: 11431423
PLoS One. 2009 Jul 31;4(7):e6465
pubmed: 19649245
Front Immunol. 2018 Feb 27;9:310
pubmed: 29535714
Nat Commun. 2015 Jul 28;6:7712
pubmed: 26218507
Vaccine. 2011 Nov 21;29(50):9385-90
pubmed: 22001120
Vaccine. 1999 Aug 6;17(23-24):3065-71
pubmed: 10462241
PLoS One. 2016 Jan 05;11(1):e0146372
pubmed: 26731269
Virology. 2013 Nov;446(1-2):56-65
pubmed: 24074567
PLoS One. 2017 Oct 26;12(10):e0186854
pubmed: 29073183
Hum Vaccin Immunother. 2016 Sep;12(9):2341-50
pubmed: 27104338
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13766-71
pubmed: 11095740
J Biol Chem. 2012 Nov 16;287(47):39776-88
pubmed: 23027866
J Virol. 2018 Oct 29;92(22):
pubmed: 30185594
J Virol. 2010 Sep;84(17):8369-88
pubmed: 20534862
Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3680-5
pubmed: 25775551
Cell Mol Immunol. 2018 May;15(5):428-437
pubmed: 29553135
Sci Rep. 2017 Apr 21;7:46426
pubmed: 28429728
Vaccine. 2003 Jun 2;21(19-20):2461-7
pubmed: 12744879
Vaccine. 2017 Dec 15;35(50):6949-6956
pubmed: 29089195
Infect Immun. 2004 Mar;72(3):1657-65
pubmed: 14977973
Vaccine. 2018 May 3;36(19):2604-2611
pubmed: 29628151
Vaccine. 2012 Jan 11;30(3):597-606
pubmed: 22120195
Viruses. 2017 Jul 13;9(7):
pubmed: 28703784
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15190-4
pubmed: 16219698
PLoS One. 2010 Oct 27;5(10):e13677
pubmed: 21060869
Cell Rep. 2014 Sep 25;8(6):1668-1676
pubmed: 25199835
Vaccine. 2016 May 17;34(23):2562-9
pubmed: 27085175
PLoS One. 2015 Aug 27;10(8):e0136862
pubmed: 26312747
Vaccine. 2004 Jul 29;22(21-22):2881-6
pubmed: 15246624
Cell Rep. 2018 May 01;23(5):1435-1447
pubmed: 29719256
Science. 2010 Aug 27;329(5995):1060-4
pubmed: 20647428
Int J Nanomedicine. 2017 Aug 23;12:6169-6184
pubmed: 28883727
J Pharm Sci. 2012 Dec;101(12):4490-500
pubmed: 22941944
J Biomed Mater Res B Appl Biomater. 2018 May;106(4):1587-1594
pubmed: 28804955
J Virol. 2008 Jul;82(13):6200-8
pubmed: 18417563
Nat Med. 2015 Sep;21(9):1065-70
pubmed: 26301691
Infect Immun. 2002 Feb;70(2):692-701
pubmed: 11796601
Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):12578-12583
pubmed: 29109276
Nat Rev Immunol. 2009 Apr;9(4):287-93
pubmed: 19247370
Science. 2013 Feb 15;339(6121):826-30
pubmed: 23258412
J Immunol. 2010 Sep 1;185(5):2989-97
pubmed: 20660705
J Infect Dis. 2013 Dec 15;208(12):1953-61
pubmed: 23904292
Am Fam Physician. 2005 Jul 1;72(1):41
pubmed: 16035682
Nat Commun. 2019 May 29;10(1):2355
pubmed: 31142746
Vaccine. 2010 Apr 19;28(18):3076-9
pubmed: 20193791
J Virol. 2010 Oct;84(19):10413-9
pubmed: 20631129
Sci Transl Med. 2010 Oct 13;2(53):53ra74
pubmed: 20944089
J Immunol. 2012 Apr 1;188(7):3088-98
pubmed: 22351935
PLoS Pathog. 2017 Oct 23;13(10):e1006682
pubmed: 29059230
Expert Rev Vaccines. 2003 Apr;2(2):219-29
pubmed: 12899573
Sci Transl Med. 2010 Mar 24;2(24):24ra21
pubmed: 20375007
Curr Opin Immunol. 2016 Oct;42:48-55
pubmed: 27268395
Biotechnol J. 2018 Apr;13(4):e1700645
pubmed: 29278302
Cell. 2015 Aug 27;162(5):1090-100
pubmed: 26279189
Hum Vaccin Immunother. 2018 Mar 4;14(3):550-564
pubmed: 29232151
Nature. 2007 Oct 18;449(7164):819-26
pubmed: 17943118
Science. 1999 Jul 30;285(5428):736-9
pubmed: 10426996
Vaccine. 2014 Apr 11;32(18):2109-16
pubmed: 24556505
PLoS One. 2011 Jan 26;6(1):e16333
pubmed: 21298114
Adv Drug Deliv Rev. 2008 May 22;60(8):915-28
pubmed: 18325628
J Infect Dis. 2008 Sep 1;198(5):642-9
pubmed: 18576945
Nature. 2013 Jul 4;499(7456):102-6
pubmed: 23698367
Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12294-9
pubmed: 25136133
J Clin Invest. 2015 Jun;125(6):2532-46
pubmed: 25938786
Mol Cell. 2013 Jul 25;51(2):226-35
pubmed: 23747010
J Immunol. 2014 May 1;192(9):4221-32
pubmed: 24659688
FEMS Immunol Med Microbiol. 2008 Mar;52(2):207-18
pubmed: 18093141
Science. 2017 Oct 6;358(6359):85-90
pubmed: 28931639
Expert Rev Vaccines. 2007 Oct;6(5):773-84
pubmed: 17931157
Nature. 2011 Sep 25;478(7370):515-8
pubmed: 21947006
Front Immunol. 2018 Apr 09;9:711
pubmed: 29686682
Influenza Other Respir Viruses. 2016 Sep;10(5):354-60
pubmed: 27426005
Science. 2006 Dec 22;314(5807):1936-8
pubmed: 17185603
Science. 2007 Aug 10;317(5839):825-8
pubmed: 17690300
Nature. 1995 Apr 6;374(6522):546-9
pubmed: 7700380
J Clin Immunol. 2004 Nov;24(6):693-701
pubmed: 15622454
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E884-93
pubmed: 26831104