Development of an mRNA-lipid nanoparticle vaccine against Lyme disease.
Borrelia burgdorferi
Lyme disease
OspA
antibody
antigen
bacteria
lipid nanoparticle
mRNA
nucleoside-modification
spirochete
vaccine
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
06 09 2023
06 09 2023
Historique:
received:
02
02
2023
revised:
19
05
2023
accepted:
28
07
2023
pmc-release:
06
09
2024
medline:
11
9
2023
pubmed:
3
8
2023
entrez:
3
8
2023
Statut:
ppublish
Résumé
Lyme disease is the most common vector-borne infectious disease in the United States, in part because a vaccine against it is not currently available for humans. We propose utilizing the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform to generate a Lyme disease vaccine like the successful clinical vaccines against SARS-CoV-2. Of the antigens expressed by Borrelia burgdorferi, the causative agent of Lyme disease, outer surface protein A (OspA) is the most promising candidate for vaccine development. We have designed and synthesized an OspA-encoding mRNA-LNP vaccine and compared its immunogenicity and protective efficacy to an alum-adjuvanted OspA protein subunit vaccine. OspA mRNA-LNP induced superior humoral and cell-mediated immune responses in mice after a single immunization. These potent immune responses resulted in protection against bacterial infection. Our study demonstrates that highly efficient mRNA vaccines can be developed against bacterial targets.
Identifiants
pubmed: 37533256
pii: S1525-0016(23)00428-8
doi: 10.1016/j.ymthe.2023.07.022
pmc: PMC10492027
pii:
doi:
Substances chimiques
Lipid Nanoparticles
0
COVID-19 Vaccines
0
Antigens, Surface
0
Bacterial Outer Membrane Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2702-2714Subventions
Organisme : NIAID NIH HHS
ID : R21 AI137433
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI153064
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI138949
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI165499
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI168312
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI142572
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI126033
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI146101
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests In accordance with the University of Pennsylvania policies and procedures and our ethical obligations as researchers, we report that D.W. is named on patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins. N.P., D.W., and Y.K.T. are named on a patent describing the use of nucleoside-modified mRNA in lipid nanoparticles as a vaccine platform. We have disclosed those interests fully to the University of Pennsylvania, and we have in place an approved plan for managing any potential conflicts arising from licensing of our patents. Y.K.T. is an employee of Acuitas Therapeutics, a company focused on the development of LNP nucleic acid delivery systems for therapeutic applications. N.P. served on the mRNA strategic advisory board of Sanofi Pasteur in 2022. N.P. is a member of the scientific advisory board of AldexChem.
Références
FEMS Immunol Med Microbiol. 2012 Oct;66(1):1-19
pubmed: 22540535
Clin Lab Med. 2010 Mar;30(1):311-28
pubmed: 20513553
Nature. 2020 Oct;586(7830):567-571
pubmed: 32756549
Nat Commun. 2018 Aug 22;9(1):3361
pubmed: 30135514
BMC Infect Dis. 2015 Oct 26;15:472
pubmed: 26503011
Microbes Infect. 2006 Mar;8(3):645-52
pubmed: 16513394
Immunity. 2010 Oct 29;33(4):451-63
pubmed: 21029957
Vaccines (Basel). 2022 May 10;10(5):
pubmed: 35632507
Ticks Tick Borne Dis. 2023 Jan;14(1):102081
pubmed: 36403322
Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2206333119
pubmed: 36322769
Emerg Infect Dis. 2021 Feb;27(2):616-619
pubmed: 33496229
Epidemiol Infect. 2007 Jan;135(1):1-8
pubmed: 16893489
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2909-13
pubmed: 7708747
Nat Rev Microbiol. 2012 Jan 09;10(2):87-99
pubmed: 22230951
Nat Commun. 2022 Aug 9;13(1):4677
pubmed: 35945226
PLoS One. 2016 Mar 03;11(3):e0150606
pubmed: 26938654
Mol Ther Nucleic Acids. 2019 Apr 15;15:26-35
pubmed: 30933724
Infect Immun. 1992 Mar;60(3):773-7
pubmed: 1541551
Sci Transl Med. 2021 Nov 17;13(620):eabj9827
pubmed: 34788080
PLoS One. 2014 Nov 19;9(11):e113294
pubmed: 25409015
N Engl J Med. 1998 Jul 23;339(4):209-15
pubmed: 9673298
Immunity. 2020 Dec 15;53(6):1281-1295.e5
pubmed: 33296685
Front Cell Infect Microbiol. 2014 Sep 26;4:136
pubmed: 25309883
Cell. 2022 Mar 17;185(6):1008-1024.e15
pubmed: 35202565
Front Med (Lausanne). 2020 Feb 25;7:57
pubmed: 32161761
Immunity. 2020 Oct 13;53(4):724-732.e7
pubmed: 32783919
Front Immunol. 2017 Feb 20;8:116
pubmed: 28265270
Infect Immun. 2001 May;69(5):3224-31
pubmed: 11292744
Infect Dis Clin North Am. 2015 Jun;29(2):187-210
pubmed: 25999219
Vector Borne Zoonotic Dis. 2017 Sep;17(9):619-629
pubmed: 28727515
Clin Infect Dis. 2011 Feb;52 Suppl 3:s259-65
pubmed: 21217173
Immunity. 2021 Dec 14;54(12):2877-2892.e7
pubmed: 34852217
J Control Release. 2015 Nov 10;217:345-51
pubmed: 26264835
Infect Immun. 2022 Jul 21;90(7):e0006222
pubmed: 35861564
Arthritis Rheum. 1977 Jan-Feb;20(1):7-17
pubmed: 836338
Open Neurol J. 2012;6:140-5
pubmed: 23248715
STAR Protoc. 2022 Dec 16;3(4):101840
pubmed: 36595931
Clin Infect Dis. 2011 Feb;52 Suppl 3:s271-5
pubmed: 21217175
Nat Rev Drug Discov. 2018 Apr;17(4):261-279
pubmed: 29326426
J Exp Med. 1996 Jan 1;183(1):271-5
pubmed: 8551231
FEMS Microbiol Rev. 2003 Oct;27(4):493-504
pubmed: 14550942
Curr Drug Targets Infect Disord. 2001 Nov;1(3):315-24
pubmed: 12455404
Infect Immun. 2020 Mar 23;88(4):
pubmed: 31932330
J Exp Med. 2018 Jun 4;215(6):1571-1588
pubmed: 29739835
Science. 1990 Oct 26;250(4980):553-6
pubmed: 2237407
Sci Immunol. 2019 Sep 20;4(39):
pubmed: 31541030
Nature. 2017 Mar 9;543(7644):248-251
pubmed: 28151488
J Biol Chem. 2012 May 11;287(20):16860-8
pubmed: 22433849
Orthop Rev (Pavia). 2011;3(2):e14
pubmed: 22053255
PLoS One. 2017 Sep 1;12(9):e0184357
pubmed: 28863166
BMC Vet Res. 2018 Oct 16;14(1):312
pubmed: 30326885
NPJ Vaccines. 2022 Jan 27;7(1):10
pubmed: 35087055
Curr Opin Immunol. 2020 Aug;65:14-20
pubmed: 32244193
NPJ Vaccines. 2022 Dec 1;7(1):155
pubmed: 36456563
N Engl J Med. 2012 Nov 15;367(20):1883-90
pubmed: 23150958
Vector Borne Zoonotic Dis. 2013 Apr;13(4):203-14
pubmed: 23428088
Curr Top Microbiol Immunol. 2022;440:111-145
pubmed: 32300916
Front Med (Lausanne). 2021 Aug 18;8:666554
pubmed: 34485323
J Clin Invest. 2020 May 1;130(5):2148-2151
pubmed: 32281948
Eur J Immunol. 2004 Nov;34(11):2977-85
pubmed: 15384078
PLoS Pathog. 2020 Nov 11;16(11):e1009030
pubmed: 33175909
Vet J. 2021 Jul;273:105676
pubmed: 34148599
Infect Immun. 1999 Aug;67(8):3929-36
pubmed: 10417158
Emerg Infect Dis. 2015 Aug;21(8):1455-7
pubmed: 26196670
NPJ Vaccines. 2021 Jun 18;6(1):84
pubmed: 34145286
Nat Rev Dis Primers. 2016 Dec 15;2:16090
pubmed: 27976670
Science. 1998 Jul 31;281(5377):703-6
pubmed: 9685265
Infect Dis Clin North Am. 2015 Jun;29(2):211-39
pubmed: 25999220
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
Vaccine. 2021 Dec 20;39(52):7661-7668
pubmed: 34862075
Clin Infect Dis. 2020 Apr 10;70(8):1768-1773
pubmed: 31620776
Sci Adv. 2023 Mar 10;9(10):eadg1036
pubmed: 36888708
Annu Rev Med. 2022 Jan 27;73:17-39
pubmed: 34669432