Threshold protective levels of serum IgG to Shigella lipopolysaccharide: re-analysis of Shigella vaccine trials data.
Conjugate vaccines
Correlate of protection
Immunological substitute
Serum IgG
Shigella
Vaccine efficacy
Journal
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN: 1469-0691
Titre abrégé: Clin Microbiol Infect
Pays: England
ID NLM: 9516420
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
received:
23
07
2022
revised:
03
10
2022
accepted:
06
10
2022
pubmed:
16
10
2022
medline:
4
3
2023
entrez:
15
10
2022
Statut:
ppublish
Résumé
Establishing a correlate of protection is essential for the development and licensure of Shigella vaccines. We examined potential threshold levels of serum IgG to Shigella lipopolysaccharide (LPS) that could predict protection against shigellosis. We performed new analyses of serologic and vaccine efficacy (VE) data from two randomized vaccine-controlled trials of the Shigella sonnei-Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conjugate conducted in young adults and children aged 1-4 years in Israel. Adults received either S. sonnei-rEPA (n = 183) or control vaccines (n = 277). Children received the S. sonnei-rEPA conjugate (n = 1384) or S. flexneri 2a-rEPA conjugate (n = 1315). VE against culture-proven shigellosis was determined. Sera were tested for IgG anti-S. sonnei LPS antibodies. We assessed the association of various levels of IgG anti-S. sonnei LPS antibodies with S. sonnei shigellosis risk using logistic regression models and the reverse cumulative distribution of IgG levels. Among adults, four vaccinees and 23 controls developed S. sonnei shigellosis; the VE was 74% (95% CI, 28-100%). A threshold of ≥1:1600 IgG anti-S. sonnei LPS titre was associated with a reduced risk of S. sonnei shigellosis and a predicted VE of 73.6% (95% CI, 65-80%). The IgG anti-S. sonnei LPS correlated with serum bactericidal titres. In children, a population-based level of 4.5 ELISA Units (EU) corresponding to 1:1072 titre, predicted VE of 63%, versus 71% observed VE in children aged 3-4 years. The predicted VE in children aged 2-4 years was 49%, consistent with the 52% observed VE. Serum IgG anti-S. sonnei LPS threshold levels can predict the degree of VE and can be used for the evaluation of new vaccine candidates.
Identifiants
pubmed: 36243351
pii: S1198-743X(22)00525-0
doi: 10.1016/j.cmi.2022.10.011
pmc: PMC9993342
pii:
doi:
Substances chimiques
Antibodies, Bacterial
0
Immunoglobulin G
0
Lipopolysaccharides
0
Shigella Vaccines
0
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
366-371Subventions
Organisme : NIAID NIH HHS
ID : R37 AI054165
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Références
Clin Infect Dis. 1992 Aug;15(2):346-61
pubmed: 1381621
BMC Med Res Methodol. 2019 Mar 6;19(1):47
pubmed: 30841856
J Infect Dis. 2011 Apr 1;203(7):969-75
pubmed: 21402548
Clin Infect Dis. 2014 Oct;59(7):933-41
pubmed: 24958238
Lancet Infect Dis. 2021 Apr;21(4):546-558
pubmed: 33186516
Clin Vaccine Immunol. 2016 Dec 5;23(12):908-917
pubmed: 27581434
Ann Appl Stat. 2019 Jun;13(2):1147-1165
pubmed: 31285781
EBioMedicine. 2021 Apr;66:103310
pubmed: 33862589
Epidemiol Infect. 2014 Dec;142(12):2583-94
pubmed: 24559503
Clin Diagn Lab Immunol. 2003 Sep;10(5):780-6
pubmed: 12965904
J Infect Dis. 1988 May;157(5):1068-71
pubmed: 3283258
Hum Vaccin Immunother. 2019;15(6):1401-1408
pubmed: 31070988
J Clin Microbiol. 1991 Feb;29(2):386-9
pubmed: 1706731
Vaccine. 2007 May 10;25(19):3816-26
pubmed: 17368878
J Infect Dis. 2022 May 4;225(9):1500-1503
pubmed: 34558631
Vaccine. 2020 Feb 24;38(9):2250-2257
pubmed: 31767462
Stat Med. 1989 Apr;8(4):431-40
pubmed: 2727467
Biometrics. 2009 Jun;65(2):530-8
pubmed: 18759836
EClinicalMedicine. 2021 Aug 13;39:101076
pubmed: 34430837
J Infect Dis. 1991 Sep;164(3):533-7
pubmed: 1869840
Vaccine. 2010 Mar 2;28(10):2231-2235
pubmed: 20056180
Vaccines (Basel). 2022 Aug 24;10(9):
pubmed: 36146457
Infect Immun. 1993 Sep;61(9):3678-87
pubmed: 8359890
Am J Epidemiol. 1991 Sep 15;134(6):614-27
pubmed: 1951266
Lancet. 1997 Jan 18;349(9046):155-9
pubmed: 9111538
J Clin Microbiol. 1989 Jan;27(1):162-7
pubmed: 2463995
Lancet Infect Dis. 2018 Nov;18(11):1229-1240
pubmed: 30266330