Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients
01/2024
Journal Article
Authors:
Howard, L. M.;
Jensen, T. L.;
Goll, J. B.;
Gelber, C. E.;
Bradley, M. D.;
Sherrod, S. D.;
Hoek, K. L.;
Yoder, S.;
Jimenez-Truque, N.;
Edwards, K.;
Creech, C. B.
Journal:
J Infect Dis
PMID:
38181048
URL:
https://www.ncbi.nlm.nih.gov/pubmed/38181048
Keywords:
As03
Adjuvant
Adversomics
Influenza
Metabolomics
Vaccination
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 two doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) one 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 post-vaccination 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.
