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Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients.

Author information

Affiliations

  • 1. Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine and Medical Center, Nashville, Tennessee, USA.
      Authors
    • Howard LM 1
    • Yoder S 1
    • Jimenez-Truque N 1
    • Edwards K 1
    • Creech CB 1
    (5 authors)
  • 2. Biomedical Data Science and Bioinformatics Department, The Emmes Company, LLC, Rockville, Maryland, USA.
      Authors
    • Jensen TL 2
    • Goll JB 2
    • Gelber CE 2
    • Bradley MD 2
    (4 authors)
  • 3. Center for Innovative Technology, Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.
      Authors
    • Sherrod SD 3
    (1 author)
  • 4. Vanderbilt Institute for Infection, Inflammation and Immunity, Vanderbilt University School of Medicine and Medical Center, Nashville, Tennessee, USA.
      Authors
    • Hoek KL 4
    (1 author)

ORCIDs linked to this article

The Journal of Infectious Diseases, 01 Sep 2024, 230(3):716-725
https://doi.org/10.1093/infdis/jiad611 PMID: 38181048 

Free full text available after 05 Jan 2025

Abstract 

Background

Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants.

Methods

Twenty healthy men and women (18-49 years of age) were randomized to receive 2 doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) 1 month apart. Urine and serum samples were collected on day 0 and on days 1, 3, and 7 following first vaccination and subjected to metabolomics analyses to identify metabolites, metabolic pathways, and metabolite clusters associated with immunization.

Results

Seventy-three differentially abundant (DA) serum and 88 urine metabolites were identified for any postvaccination day comparison. Pathway analysis revealed enrichment of tryptophan, tyrosine, and nicotinate metabolism in urine and serum among IIV-AS03 recipients. Increased urine abundance of 4-vinylphenol sulfate on day 1 was associated with serologic response based on hemagglutination inhibition responses. In addition, 9 DA urine metabolites were identified in participants with malaise compared to those without.

Conclusions

Our findings suggest that tryptophan, tyrosine, and nicotinate metabolism are upregulated among IIV-AS03 recipients compared with IIV alone. Metabolites within these pathways may serve as measures of immunogenicity and may provide mechanistic insights for adjuvanted vaccines.

Clinical trials registration

NCT01573312.

Full text links 

Read article at publisher's site: https://doi.org/10.1093/infdis/jiad611

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Funding 

Funders who supported this work.

NCATS NIH HHS (1)

NIH HHS (1)

National Center for Advancing Translational Sciences

    National Institute of Allergy and Infectious Diseases

      National Institutes of Health (2)