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J Infect Dis . Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients

tetano

Editor, Senior Moderator
J Infect Dis


. 2024 Jan 5:jiad611.
doi: 10.1093/infdis/jiad611. Online ahead of print. Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients

Leigh M Howard[SUP] 1 [/SUP], Travis L Jensen[SUP] 2 [/SUP], Johannes B Goll[SUP] 2 [/SUP], Casey E Gelber[SUP] 2 [/SUP], Matthew D Bradley[SUP] 2 [/SUP], Stacy D Sherrod[SUP] 3 [/SUP], Kristen L Hoek[SUP] 4 [/SUP], Sandra Yoder[SUP] 1 [/SUP], Natalia Jimenez-Truque[SUP] 1 [/SUP], Kathryn Edwards[SUP] 1 [/SUP], C Buddy Creech[SUP] 1 [/SUP]



Affiliations
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.

Keywords: AS03; Adjuvant; Adversomics; Influenza; Metabolomics; Vaccination.

 
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