» Articles » PMID: 34374425

Functional Antibodies and Innate Immune Responses to WRSS1, a Live Oral Shigella Sonnei Vaccine Candidate, in Bangladeshi Adults and Children

Overview
Journal J Infect Dis
Date 2021 Aug 10
PMID 34374425
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

Background: We demonstrated in a randomized placebo-controlled trial that WRSS1, a live oral Shigella sonnei vaccine candidate, is safe in Bangladeshi adults and children, and elicits antigen-specific antibodies. Here, we describe functional antibody and innate immune responses to WRSS1.

Methods: Adults (18-39 years) and children (5-9 years) received 3 doses of 3 × 105 or 3 × 106 colony forming units (CFU) of WRSS1 or placebo, 4 weeks apart; children additionally received 3 × 104 CFU. Blood and stool were collected at baseline and 7 days after each dose. Functional antibodies were measured using serum bactericidal antibody (SBA) assay. Cytokine/chemokine concentrations were measured in lymphocyte cultures. Host defense peptides LL-37, HBD-1, and HD-5 were analyzed in plasma and stool.

Results: Children showed increased SBA titers over baseline after the third dose of 3 × 106 CFU (P = .048). Significant increases of Th-17 and proinflammatory cytokines (TNF-α, G-CSF, MIP-1β), and reduction of anti-inflammatory and Th2 cytokines (IL-10, IL-13, GM-CSF) were observed in children. Plasma HBD-1 and LL-37 decreased in children after vaccination but were increased/unchanged in adults.

Conclusions: Functional antibodies and Th1/Th17 cytokine responses in children may serve as important indicators of immunogenicity and protective potential of WRSS1. Clinical Trials Registration: NCT01813071.

Citing Articles

Vaccines: The Continuing Unmet Challenge.

Lu T, Das S, Howlader D, Picking W, Picking W Int J Mol Sci. 2024; 25(8).

PMID: 38673913 PMC: 11050647. DOI: 10.3390/ijms25084329.


Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine.

Conti V, Rossi O, Clarkson K, Mancini F, Nakakana U, Sarakinou E NPJ Vaccines. 2024; 9(1):56.

PMID: 38459072 PMC: 10923941. DOI: 10.1038/s41541-024-00822-2.


Age-dependent acquisition of IgG antibodies to serotypes-a retrospective analysis of seroprevalence in Kenyan children with implications for infant vaccination.

Kapulu M, Muthumbi E, Otieno E, Rossi O, Ferruzzi P, Necchi F Front Immunol. 2024; 15:1340425.

PMID: 38361949 PMC: 10867106. DOI: 10.3389/fimmu.2024.1340425.


Oral immunization with WRSs2 and WRSs3 vaccine strains elicits systemic and mucosal antibodies with functional anti-microbial activity.

Shrivastava S, Agnememel A, Ndungo E, Islam D, Liang Y, Frenck Jr R mSphere. 2023; 9(1):e0041923.

PMID: 38132716 PMC: 10826362. DOI: 10.1128/msphere.00419-23.


Refining Immunogenicity through Intradermal Delivery of Outer Membrane Vesicles against in Mice.

Pastor Y, Calvo A, Salvador-Erro J, Gamazo C Int J Mol Sci. 2023; 24(23).

PMID: 38069232 PMC: 10706920. DOI: 10.3390/ijms242316910.


References
1.
Kotloff K, Noriega F, Samandari T, Sztein M, Losonsky G, Nataro J . Shigella flexneri 2a strain CVD 1207, with specific deletions in virG, sen, set, and guaBA, is highly attenuated in humans. Infect Immun. 2000; 68(3):1034-9. PMC: 97245. DOI: 10.1128/IAI.68.3.1034-1039.2000. View

2.
Dong C . TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008; 8(5):337-48. DOI: 10.1038/nri2295. View

3.
Islam D, Bardhan P, Lindberg A, Christensson B . Shigella infection induces cellular activation of T and B cells and distinct species-related changes in peripheral blood lymphocyte subsets during the course of the disease. Infect Immun. 1995; 63(8):2941-9. PMC: 173400. DOI: 10.1128/iai.63.8.2941-2949.1995. View

4.
Raqib R, Sarker P, Bergman P, Ara G, Lindh M, Sack D . Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proc Natl Acad Sci U S A. 2006; 103(24):9178-83. PMC: 1482586. DOI: 10.1073/pnas.0602888103. View

5.
Toapanta F, Bernal P, Kotloff K, Levine M, Sztein M . T cell mediated immunity induced by the live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S in humans. J Transl Med. 2018; 16(1):61. PMC: 5851169. DOI: 10.1186/s12967-018-1439-1. View