A Recombinant Alpha-Like Protein Subunit Vaccine (GBS-NN) Provides Protection in Murine Models of Group B Streptococcus Infection.
Streptococcus agalactiae
Rib
alpha-like proteins
group B Streptococcus
intranasal infection
maternal vaccination
neonate
pregnancy
surface proteins
vaccine
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
12 08 2022
12 08 2022
Historique:
received:
02
03
2022
accepted:
11
04
2022
pubmed:
17
4
2022
medline:
16
8
2022
entrez:
16
4
2022
Statut:
ppublish
Résumé
Group B Streptococcus (GBS) transmission during pregnancy causes preterm labor, stillbirths, fetal injury, or neonatal infections. Rates of adult infections are also rising. The GBS-NN vaccine, engineered by fusing N-terminal domains of GBS Alpha C and Rib proteins, is safe in healthy, nonpregnant women, but further assessment is needed for use during pregnancy. Here, we tested GBS-NN vaccine efficacy using mouse models that recapitulate human GBS infection outcomes. Following administration of GBS-NN vaccine or adjuvant, antibody profiles were compared by ELISA. Vaccine efficacy was examined by comparing infection outcomes in GBS-NN vaccinated versus adjuvant controls during systemic and pregnancy-associated infections, and during intranasal infection of neonatal mice following maternal vaccination. Vaccinated mice had higher GBS-NN-specific IgG titers versus controls. These antibodies bound alpha C and Rib on GBS clinical isolates. Fewer GBS were recovered from systemically challenged vaccinated mice versus controls. Although vaccination did not eliminate GBS during ascending infection in pregnancy, vaccinated dams experienced fewer in utero fetal deaths. Additionally, maternal vaccination prolonged neonatal survival following intranasal GBS challenge. These findings demonstrate GBS-NN vaccine efficacy in murine systemic and perinatal GBS infections and suggest that maternal vaccination facilitates the transfer of protective antibodies to neonates.
Sections du résumé
BACKGROUND
Group B Streptococcus (GBS) transmission during pregnancy causes preterm labor, stillbirths, fetal injury, or neonatal infections. Rates of adult infections are also rising. The GBS-NN vaccine, engineered by fusing N-terminal domains of GBS Alpha C and Rib proteins, is safe in healthy, nonpregnant women, but further assessment is needed for use during pregnancy. Here, we tested GBS-NN vaccine efficacy using mouse models that recapitulate human GBS infection outcomes.
METHODS
Following administration of GBS-NN vaccine or adjuvant, antibody profiles were compared by ELISA. Vaccine efficacy was examined by comparing infection outcomes in GBS-NN vaccinated versus adjuvant controls during systemic and pregnancy-associated infections, and during intranasal infection of neonatal mice following maternal vaccination.
RESULTS
Vaccinated mice had higher GBS-NN-specific IgG titers versus controls. These antibodies bound alpha C and Rib on GBS clinical isolates. Fewer GBS were recovered from systemically challenged vaccinated mice versus controls. Although vaccination did not eliminate GBS during ascending infection in pregnancy, vaccinated dams experienced fewer in utero fetal deaths. Additionally, maternal vaccination prolonged neonatal survival following intranasal GBS challenge.
CONCLUSIONS
These findings demonstrate GBS-NN vaccine efficacy in murine systemic and perinatal GBS infections and suggest that maternal vaccination facilitates the transfer of protective antibodies to neonates.
Identifiants
pubmed: 35429401
pii: 6569354
doi: 10.1093/infdis/jiac148
pmc: PMC9890916
doi:
Substances chimiques
Protein Subunits
0
Streptococcal Vaccines
0
Vaccines, Subunit
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
177-187Subventions
Organisme : NIAID NIH HHS
ID : R01 AI152268
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007509
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI055396
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Déclaration de conflit d'intérêts
Potential conflicts of interest. B. J.-L. reports personal fees and grants from MinervaX A/S during the conduct of the study. P. B. F. reports personal fees from MinervaX A/S during the conduct of the study, personal fees from MinervaX A/S outside this submitted work, and has patent applications relating to the use of GBS-NN as a vaccine candidate. All other authors report no potential conflicts.
Références
Clin Infect Dis. 2017 Nov 06;65(suppl_2):S143-S151
pubmed: 29117324
Chemistry. 2020 Jun 2;26(31):7018-7025
pubmed: 32058627
Lancet Infect Dis. 2021 Feb;21(2):263-274
pubmed: 32891191
Adv Exp Med Biol. 1997;418:855-7
pubmed: 9331787
Clin Infect Dis. 2020 Jun 10;70(12):2570-2579
pubmed: 31394574
Emerg Infect Dis. 2016 Nov;22(11):1941-1944
pubmed: 27767925
J Exp Med. 1975 Jul 1;142(1):165-79
pubmed: 1097573
Vaccine. 2020 Oct 14;38(44):6930-6940
pubmed: 32883555
Sci Rep. 2016 Aug 12;6:31578
pubmed: 27515230
Clin Infect Dis. 2017 Nov 06;65(suppl_2):S200-S219
pubmed: 29117332
Vaccine. 2019 Nov 28;37(50):7307-7314
pubmed: 28017431
Clin Infect Dis. 2021 Mar 15;72(6):1004-1013
pubmed: 32060499
J Infect. 2018 May;76(5):449-456
pubmed: 29374589
Vaccine. 2016 Apr 4;34(15):1786-91
pubmed: 26928074
Epidemiol Infect. 2014 Jan;142(1):208-10
pubmed: 23561305
JAMA Intern Med. 2019 Apr 1;179(4):479-488
pubmed: 30776079
Lancet Infect Dis. 2016 May;16(5):546-555
pubmed: 26869376
Sci Rep. 2018 Feb 7;8(1):2593
pubmed: 29416049
Lancet Infect Dis. 2016 Aug;16(8):923-34
pubmed: 27139805
Glycoconj J. 2021 Aug;38(4):447-457
pubmed: 33956253
Cell Microbiol. 2002 Nov;4(11):751-8
pubmed: 12427097
J Infect Dis. 2012 Dec 1;206(11):1745-52
pubmed: 23002446
Arch Dis Child Fetal Neonatal Ed. 2006 Nov;91(6):F403-8
pubmed: 17056838
mBio. 2016 Jun 28;7(3):
pubmed: 27353757
Cell Host Microbe. 2007 Dec 13;2(6):427-34
pubmed: 18078694
Eur J Clin Microbiol Infect Dis. 2014 Jul;33(7):1155-62
pubmed: 24469423
Clin Infect Dis. 2017 Nov 06;65(suppl_2):S152-S159
pubmed: 29117325
Clin Infect Dis. 2017 Nov 06;65(suppl_2):S160-S172
pubmed: 29117326
J Exp Med. 1993 Jun 1;177(6):1593-603
pubmed: 8496678
J Infect Dis. 2020 Mar 2;221(6):943-947
pubmed: 31641758
J Biol Chem. 2007 Apr 6;282(14):10526-36
pubmed: 17259175
Clin Infect Dis. 2019 May 30;68(12):2079-2086
pubmed: 30281066
J Infect Dis. 1999 Jan;179(1):142-50
pubmed: 9841833
Nat Commun. 2020 Mar 20;11(1):1502
pubmed: 32198389
Microbiology (Reading). 2007 Dec;153(Pt 12):4039-4049
pubmed: 18048918
J Clin Microbiol. 1982 Jul;16(1):141-4
pubmed: 6125528
BMC Infect Dis. 2020 Apr 22;20(1):302
pubmed: 32321444
J Clin Invest. 1996 Nov 15;98(10):2308-14
pubmed: 8941648
J Infect Dis. 2000 Oct;182(4):1129-38
pubmed: 10979909
J Biol Chem. 2004 Jun 4;279(23):24714-23
pubmed: 15044471
Clin Infect Dis. 2017 Nov 06;65(suppl_2):S100-S111
pubmed: 29117327
Clin Microbiol Rev. 2005 Jan;18(1):102-27
pubmed: 15653821
Clin Infect Dis. 2017 Nov 06;65(suppl_2):S133-S142
pubmed: 29117329
Obstet Gynecol. 2016 Feb;127(2):213-21
pubmed: 26942345
Hum Vaccin Immunother. 2015;11(3):755-60
pubmed: 25751765
Infect Immun. 2001 Nov;69(11):6696-701
pubmed: 11598040
Vaccine. 2021 Jul 22;39(32):4489-4499
pubmed: 34215454
Clin Infect Dis. 2017 Nov 13;65(11):1897-1904
pubmed: 29029127
J Infect Dis. 2019 Jun 5;220(1):105-115
pubmed: 30778554
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13251-6
pubmed: 9371832