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Author Notes:

Correspondence: Savita Pahwa, spahwa@med.miami.edu

Author contributions: SP, AW, CC, R-PS, and MC were involved in conception of the work. CS, AP, VG, and AF-M were involved in data collection. LD, CS, AP, VG, AF-M, R-PS, MC, and SP, data analysis and interpretation. LD, MC, and SP drafted the article. LD, CS, VG, AW, CC, R-PS, MC, and SP provided critical revision of the article. All authors contributed to the article and approved the submitted version.

Acknowledgements: We acknowledge members of the P1088 Protocol Team which include: Patricia M. Flynn, MD, MS, St. Jude Children’s Research Hospital, Memphis TN; Sharon Nachman, MD, SUNY Health Science Center at Stony Brook, Stony Brook, NY; Petronella Muresan, MS, Statistical and Data Analysis Center, Harvard School Public Health, Boston, MA;

Terence Fenton, Ed D, Statistical and Data Analysis Center, Harvard School Public Health, Boston, MA; Stephen A. Spector, MD, University of California, San Diego, La Jolla, CA and Rady Children’s Hospital; Coleen K. Cunningham, MD, Duke University Medical Center, Durham, NC; Robert Pass, MD, University of Alabama at Birmingham, Birmingham, AL; Ram Yogev, MD, Children’s Memorial Hospital and Feinberg School of Medicine Northwestern University Medical School, Chicago, IL;

Sandra Burchett, MD, MS, Children’s Hospital Boston, Boston, MA; Barbara Heckman, BS, Frontier Science and Technology Research Foundation, Buffalo, NY; Anthony Bloom, BA, Frontier Science and Technology Research Foundation, Buffalo, NY; L. Jill Utech, RN, MSN, CCRC, St. Jude Children’s Research Hospital, Memphis, TN;

Patricia Anthony, BS, CLS, University of Southern California, Keck School of Medicine, Los Angeles, CA; Elizabeth Petzold, PhD, Social and Scientific Systems, Silver Spring, MD; Wende Levy, RN, MS, Social and Scientific Systems, Silver Spring, MD; Jennifer Bryant, MPA, Westat, Rockville, MD;

George K. Siberry, MD, MPH, Pediatric Adolescent and Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Development, Bethesda, MD; Ruth Ebiasah, Pharm D, MS, R Ph., Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD;

Judi Miller, RN, BSN, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Ed Handelsman, MD, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Adriana Weinberg, MD, University of Colorado, Denver, Aurora, CO.

Disclosures: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Research Funding:

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].

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.

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.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • pandemic
  • influenza
  • vaccine
  • pediatric
  • HIV
  • microarray
  • systems vaccinology
  • Metabolic stress
  • Cells

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

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Journal Title:

Frontiers in Immunology

Volume:

Volume 12

Publisher:

, Pages 639358-639358

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2021 de Armas, George, Filali-Mouhim, Steel, Parmigiani, Cunningham, Weinberg, Trautmann, Sekaly, Cameron and Pahwa.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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