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Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients


AUTHORS

Howard LM , Jensen TL , Goll JB , Gelber CE , Bradley MD , Sherrod SD , Hoek KL , Yoder S , Jimenez-Truque N , Edwards K , Creech CB , . The Journal of infectious diseases. 2024 1 5; ().

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.



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