A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 09 2023
12 09 2023
Historique:
received:
18
05
2022
accepted:
02
09
2023
medline:
14
9
2023
pubmed:
13
9
2023
entrez:
12
9
2023
Statut:
epublish
Résumé
Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.
Identifiants
pubmed: 37699929
doi: 10.1038/s41467-023-41376-6
pii: 10.1038/s41467-023-41376-6
pmc: PMC10497546
doi:
Substances chimiques
Antibodies, Neutralizing
0
mRNA Vaccines
0
Glycoproteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5603Informations de copyright
© 2023. Springer Nature Limited.
Références
Vaccines (Basel). 2013 Jul 18;1(3):262-77
pubmed: 26344112
Emerg Infect Dis. 2010 Oct;16(10):1598-600
pubmed: 20875288
Vaccine. 2019 Aug 23;37(36):5404-5413
pubmed: 31331770
Sci Transl Med. 2019 Oct 2;11(512):
pubmed: 31578242
Hum Vaccin Immunother. 2019;15(9):2066-2074
pubmed: 31071008
Nucleic Acids Res. 2010 Sep;38(17):5884-92
pubmed: 20457754
Sci Adv. 2020 Jun 24;6(26):eaaz6893
pubmed: 32637598
J Clin Invest. 2020 Jan 2;130(1):539-551
pubmed: 31820871
Vaccine. 2007 May 16;25(20):4093-102
pubmed: 17360080
Nat Commun. 2016 May 10;7:11544
pubmed: 27161536
Immunity. 2005 Aug;23(2):165-75
pubmed: 16111635
NPJ Vaccines. 2018 Mar 20;3:11
pubmed: 29581897
Trends Mol Med. 2013 Dec;19(12):705-13
pubmed: 24138818
J Infect Dis. 2018 May 25;217(12):1957-1966
pubmed: 29800368
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2020 Jan;63(1):65-73
pubmed: 31776599
Mol Ther. 2008 Nov;16(11):1833-40
pubmed: 18797453
Viruses. 2012 Oct 09;4(10):2031-48
pubmed: 23202452
Hum Vaccin Immunother. 2017 Dec 2;13(12):2902-2911
pubmed: 29045192
Cell Rep. 2023 May 30;42(5):112524
pubmed: 37209096
Curr Opin Virol. 2019 Aug;37:84-90
pubmed: 31357140
Mol Ther Nucleic Acids. 2019 Apr 15;15:1-11
pubmed: 30785039
Emerg Infect Dis. 2019 Feb;25(2):245-248
pubmed: 30666924
J Immunol Methods. 2019 Nov;474:112654
pubmed: 31421081
J Infect Dis. 1980 May;141(5):580-9
pubmed: 6768812
Curr Opin Virol. 2019 Aug;37:97-104
pubmed: 31401518
Am J Trop Med Hyg. 1970 Jul;19(4):695-6
pubmed: 4987549
Epidemiol Rev. 2019 Jan 31;41(1):28-33
pubmed: 31673694
Immunity. 2021 Sep 14;54(9):2133-2142.e3
pubmed: 34453880
Cell Host Microbe. 2022 Dec 14;30(12):1759-1772.e12
pubmed: 36400021
N Engl J Med. 2021 Nov 4;385(19):1761-1773
pubmed: 34525277
Nat Commun. 2018 Oct 11;9(1):4223
pubmed: 30310067
Curr Top Microbiol Immunol. 2023;440:87-109
pubmed: 33861373
Viruses. 2020 Mar 14;12(3):
pubmed: 32183319
J Virol. 2018 May 29;92(12):
pubmed: 29593043
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Vet Pathol. 2017 May;54(3):549-562
pubmed: 28438110
Front Microbiol. 2015 Oct 01;6:1037
pubmed: 26483768
Science. 2013 May 31;340(6136):1113-7
pubmed: 23618766
Science. 2017 Jun 2;356(6341):923-928
pubmed: 28572385
PLoS Med. 2005 Jun;2(6):e183
pubmed: 15971954
Science. 2018 Mar 16;359(6381):1201-1202
pubmed: 29590055
Nat Med. 2017 Oct;23(10):1146-1149
pubmed: 28869611
Viruses. 2021 Mar 15;13(3):
pubmed: 33804206
Sci Rep. 2020 Sep 29;10(1):16030
pubmed: 32994446
N Engl J Med. 2018 Nov 1;379(18):1745-1753
pubmed: 30332564
J Infect Dis. 2018 Jan 17;217(3):451-455
pubmed: 29281112
J Control Release. 2015 Nov 10;217:337-44
pubmed: 26342664
N Engl J Med. 2021 Feb 4;384(5):470-471
pubmed: 33378607
Antiviral Res. 2016 Sep;133:218-222
pubmed: 27531367
Am J Trop Med Hyg. 1996 Dec;55(6):661-6
pubmed: 9025695
Curr Opin Virol. 2019 Aug;37:118-122
pubmed: 31479989
Microbes Infect. 2002 Jan;4(1):43-50
pubmed: 11825774
MMWR Morb Mortal Wkly Rep. 2004 Oct 1;53(38):894-7
pubmed: 15457145
Sci Rep. 2015 Oct 12;5:14775
pubmed: 26456301
Cell. 2019 Aug 8;178(4):1004-1015.e14
pubmed: 31398326