678 - Bacille Calmette Guérin (BCG) and Hepatitis B vaccine (HBV) induce distinct changes in the human neonatal plasma metabolome

Publication Number: 678.3696

Jing Chen, Boston Children's Hospital, Boston, MA, United States; Caitlin Syphurs, Boston Children's Hospital, Boston, MA, United States; Annmarie Hoch, Boston Children's Hospital, Cambridge, MA, United States; Asimenia Angelidou, Harvard Medical School, Boston, MA, United States; Olubukola T. Idoko, LSHTM, Lyon, Rhone-Alpes, France; Casey Shannon, PROOF Centre, Vancouver, BC, Canada; Rym Ben-Othman, RAN BIOLINKS, Toronto, ON, Canada; Kinga K. Smolen, Boston Children's Hospital, Boston, MA, United States; Kerry McEnaney, Boston Children's Hospital, Boston, MA, United States; Oludare A. Odumade, University of Minnesota Medical School, Minneapolis, MN, United States; Jessica Lasky-Su, Brigham and Women's Hoapital, Boston, MA, United States; Scott J. Tebbutt, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Al Ozonoff, Harvard Medical School, Boston, MA, United States; Tobias R. Kollmann, Dalhousie University, Halifax, NS, Canada; Beate Kampmann, Charite Universitatsmedizin, Berlin, Berlin, Germany; Ofer Levy, Precision Vaccines Program, Boston Children's Hospital, Boston, MA, United States; Joann Diray-Arce, Harvard Medical School, Boston, MA, United States

Background: Infectious diseases lead to ~2 million infant deaths globally each year. While immunization significantly reduces infection-related mortality, few vaccines are optimized for early life. The Expanded Program on Immunization Consortium (EPIC)-002 study aims to identify vaccine-specific “OMIC” signatures correlating with immunogenicity in newborns. Analyzing plasma metabolomic profiles before and after vaccination may reveal markers associated with protective immune responses, aiding vaccine development tailored to early-life immunity.

Objective: To identify and characterize metabolic pathways and metabolites in newborns that change following vaccination and correlate with immunogenicity, providing insights into immune activation and vaccine efficacy.

Design/Methods: The EPIC-002 study evaluated plasma metabolomic profiles in 684 newborns (1260 samples) from The Gambia. Participants were randomized to receive the Hepatitis B vaccine (HBV), Bacille Calmette-Guérin (BCG) vaccine, or both at birth (day of life 0, DOL0) or with delayed vaccination on DOL7. Blood was collected at baseline and with either DOL1, DOL3, or DOL7 per participant's randomization group. Samples were also collected to assess anti-hepatitis B surface antigen (HepB Ab) responses at DOL30 and DOL128. Global metabolic profiling was performed using mass spectrometry to characterize metabolic responses. Variability was assessed and regression models were used to analyze metabolomic changes. Associations between baseline metabolites and the HepB Ab response were also evaluated.

Results: Significant plasma metabolite changes were observed in HBV, BCG, and combined vaccine groups compared with the delayed group. Sixteen metabolites were altered across comparisons; 11 were associated with lipid pathways (e.g., fatty acid, dicarboxylates) and 5 with amino acid pathways, including tryptophan metabolism. The HBV group showed 36 distinct alterations, mainly in fatty acids and acylcarnitines, while the BCG group showed 45 distinct changes in amino acid metabolism (e.g., urea cycle, arginine, and proline). The combined group had 19 distinct alterations in lipids and peptides. Additionally, 98 metabolites, mostly lipid-associated, were significantly associated with the HepB Ab response.

Conclusion(s): Hepatitis B and Bacille Calmette-Guérin vaccines induce distinct metabolic changes in the plasma, including lipid pathways that correlate with the Hepatitis B antibody response. These findings suggest that specific metabolic changes may contribute to vaccine immunogenicity and provide insights for understanding vaccine-induced immune responses in newborns.

Figure 1: Study Design and Vaccine-Induced Metabolite Changes in Newborns
Fig1.jpeg(A) Study design overview: Metabolomic profiling was conducted on 1,260 plasma samples from 687 newborns in The Gambia, examining responses across four different vaccine types. Samples were profiled using mass spectrometry-based metabolomic analysis.
(B) Volcano plots display significant metabolite changes post-vaccination for HBV and BCG vaccines. Unique and overlapping significant metabolites across vaccine types are illustrated in the Venn diagram, highlighting metabolic pathways impacted by each vaccine.

Figure 2: Pathway-Level Analysis of Metabolite Changes Post-Vaccination
Fig2.jpegFigure 2: Pathway-Level Analysis of Metabolite Changes Post-Vaccination
The plot shows pathway-level responses of significant metabolites for BCG, HBV, and HBV+BCG vaccine groups. Each triangle represents a significant metabolite, with the direction (upward or downward) indicating positive or negative coefficients, respectively. The size of each triangle corresponds to the impact ratio, reflecting the proportion of significant metabolites within each pathway. Pathways are color-coded by broader metabolite classes (e.g., amino acids, lipids).