Publication

Transcriptional and Immunologic Correlates of Response to Pandemic Influenza Vaccine in Aviremic, HIV-Infected Children

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Last modified
  • 05/21/2025
Type of Material
Authors
    Lesley R. de Armas, University of MiamiVarghese George, University of MiamiAbdelali Filali-Mouhim, University of MontrealCourtney Steel, Vaccine & Gene Therapy Institute of FloridaAnita Parmigiani, University of MiamiColeen K. Cunningham, Duke UniversityAdriana Weinberg, University of ColoradoLydie Trautmann, Oregon Health & Science UniversityRafick-Pierre Sekaly, Emory UniversityMark J. Cameron, Case Western Reserve UniversitySavita Pahwa, University of Miami
Language
  • English
Date
  • 2021-03-25
Publisher
  • Frontiers Media S.A.
Publication Version
Copyright Statement
  • © 2021 de Armas, George, Filali-Mouhim, Steel, Parmigiani, Cunningham, Weinberg, Trautmann, Sekaly, Cameron and Pahwa.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 12
Start Page
  • 639358
End Page
  • 639358
Grant/Funding Information
  • Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9–001/HHSN267200800001C).
  • This publication was made possible by support for the Miami Center for AIDS Research (CFAR) at the University of Miami Miller School of Medicine funded by a grant (P30AI073961) and to SP (R01AI108472) from the National Institutes of Health (NIH) and R01, which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NIDDK, NIGMS, FIC AND OAR.
  • This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group.
  • This work was funded by an ARRA IMPACT grant to SP.
  • Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH) [AI068632].
Supplemental Material (URL)
Abstract
  • People living with HIV (PWH) often exhibit poor responses to influenza vaccination despite effective combination anti-retroviral (ART) mediated viral suppression. There exists a paucity of data in identifying immune correlates of influenza vaccine response in context of HIV infection that would be useful in improving its efficacy in PWH, especially in younger individuals. Transcriptomic data were obtained by microarray from whole blood isolated from aviremic pediatric and adolescent HIV-infected individuals (4-25 yrs) given two doses of Novartis/H1N1 09 vaccine during the pandemic H1N1 influenza outbreak. Supervised clustering and gene set enrichment identified contrasts between individuals exhibiting high and low antibody responses to vaccination. High responders exhibited hemagglutination inhibition antibody titers >1:40 post-first dose and 4-fold increase over baseline. Baseline molecular profiles indicated increased gene expression in metabolic stress pathways in low responders compared to high responders. Inflammation-related and interferon-inducible gene expression pathways were higher in low responders 3 wks post-vaccination. The broad age range and developmental stage of participants in this study prompted additional analysis by age group (e.g. <13yrs and ≥13yrs). This analysis revealed differential enrichment of gene pathways before and after vaccination in the two age groups. Notably, CXCR5, a homing marker expressed on T follicular helper (Tfh) cells, was enriched in high responders (>13yrs) following vaccination which was accompanied by peripheral Tfh expansion. Our results comprise a valuable resource of immune correlates of vaccine response to pandemic influenza in HIV infected children that may be used to identify favorable targets for improved vaccine design in different age groups.
Author Notes
Keywords
Research Categories
  • Biology, Cell
  • Biology, Neuroscience
  • Biology, Genetics
  • Health Sciences, Immunology

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