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Perinatally HIV-infected children (PHIV), despite successful antiretroviral therapy, present suboptimal responses to vaccinations compared to healthy-controls (HC). Here we investigated phenotypic and transcriptional signatures of H1N1-specific B-cells (H1N1-Sp) in PHIV, differentially responding to trivalent-influenza-vaccine (TIV), and HC. Patients were categorized in responders (R) and non-responders (NR) according to hemagglutination-inhibition-assay at baseline and 21 days after TIV. No differences in H1N1-Sp frequencies were found between groups. H1N1-Sp transcriptional analysis revealed a distinct signature between PHIV and HC. NR presented higher PIK3C2B and NOD2 expression compared to R, confirmed by downregulation of PIK3C2B in resting-memory of R after H1N1 in-vitro stimulation. In conclusion this study confirms that qualitative rather than quantitative analyses are needed to characterize immune responses in PHIV. These results further suggest that higher PIK3C2B in H1N1-Sp of NR is associated with lower H1N1 immunogenicity and may be targeted by future modulating strategies to improve TIV responses in PHIV.

Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists.

Titel:	Higher PIK3C2B gene expression of H1N1+ specific B-cells is associated with lower H1N1 immunogenicity after trivalent influenza vaccination in HIV infected children.
Autor/in / Beteiligte Person:	Cotugno, N ; Zicari, S ; Morrocchi, E ; de Armas LR ; Pallikkuth, S ; Rinaldi, S ; Ruggiero, A ; Manno, EC ; Zangari, P ; Chiriaco, M ; Bernardi, S ; Andrews, SF ; Cagigi, A ; Rossi, P ; McDermott, AB ; Pahwa, S ; Palma, P
Zeitschrift:	Clinical immunology (Orlando, Fla.), Jg. 215 (2020-06-01), S. 108440
Veröffentlichung:	Orlando, FL : Academic Press, c1999-, 2020
Medientyp:	academicJournal
ISSN:	1521-7035 (electronic)
DOI:	10.1016/j.clim.2020.108440
Schlagwort:	Adolescent Antibodies, Viral immunology Class II Phosphatidylinositol 3-Kinases genetics Down-Regulation genetics Down-Regulation immunology Female Gene Expression genetics Hemagglutination Inhibition Tests methods Humans Male Transcription, Genetic genetics Transcription, Genetic immunology Vaccination methods B-Lymphocytes immunology Class II Phosphatidylinositol 3-Kinases immunology Gene Expression immunology HIV Infections immunology Immunogenicity, Vaccine immunology Influenza A Virus, H1N1 Subtype immunology Influenza Vaccines immunology Influenza, Human immunology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Clin Immunol] 2020 Jun; Vol. 215, pp. 108440. <i>Date of Electronic Publication: </i>2020 Apr 21. MeSH Terms: B-Lymphocytes / immunology ; Class II Phosphatidylinositol 3-Kinases / immunology ; Gene Expression / immunology ; HIV Infections / immunology ; Immunogenicity, Vaccine / immunology ; Influenza A Virus, H1N1 Subtype / immunology ; Influenza Vaccines / immunology ; Influenza, Human / immunology ; Adolescent ; Antibodies, Viral / immunology ; Class II Phosphatidylinositol 3-Kinases / genetics ; Down-Regulation / genetics ; Down-Regulation / immunology ; Female ; Gene Expression / genetics ; Hemagglutination Inhibition Tests / methods ; Humans ; Male ; Transcription, Genetic / genetics ; Transcription, Genetic / immunology ; Vaccination / methods References: J Virus Erad. 2015;1:153-158. (PMID: 26807446) ; Hum Vaccin Immunother. 2014;10(7):2083-8. (PMID: 25424820) ; Sci Rep. 2019 Feb 21;9(1):2482. (PMID: 30792481) ; J Allergy Clin Immunol. 2015 Mar;135(3):753-61.e2. (PMID: 25175493) ; J Allergy Clin Immunol. 2008 Jul;122(1):12-9; quiz 20-1. (PMID: 18547629) ; J Allergy Clin Immunol. 2014 Feb;133(2):592-4. (PMID: 24290278) ; Immunity. 2006 Oct;25(4):545-57. (PMID: 17000121) ; J Clin Invest. 2014 Jul;124(7):3252-62. (PMID: 24892810) ; Open Biol. 2014 Dec;4(12):. (PMID: 25520185) ; J Immunol. 2017 Mar 1;198(5):1995-2005. (PMID: 28130496) ; Lancet Infect Dis. 2004 Aug;4(8):510-8. (PMID: 15288824) ; Immunol Rev. 2010 Sep;237(1):55-71. (PMID: 20727029) ; J Immunol. 2008 Nov 15;181(10):7316-23. (PMID: 18981154) ; J Immunol Res. 2019 Apr 28;2019:8732191. (PMID: 31183393) ; J Virol. 2014 Apr;88(8):4047-57. (PMID: 24501410) ; Sci Rep. 2015 Jul 08;5:12018. (PMID: 26153766) ; Science. 2013 Nov 15;342(6160):866-71. (PMID: 24136356) ; Sci Rep. 2016 Mar 17;6:23277. (PMID: 26983806) ; AIDS. 2020 Apr 1;34(5):669-680. (PMID: 32167989) ; Front Immunol. 2018 May 15;9:975. (PMID: 29867955) ; Blood. 2012 Aug 2;120(5):985-93. (PMID: 22692510) ; Cell Rep. 2015 Dec 1;13(9):1881-94. (PMID: 26655903) ; Blood. 2006 Sep 1;108(5):1580-7. (PMID: 16645169) ; Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792) ; Sci Rep. 2016 May 25;6:26478. (PMID: 27220898) ; Vaccine. 2017 Oct 27;35(45):6103-6111. (PMID: 28987439) ; Mol Cell Biol. 2007 Nov;27(22):7906-17. (PMID: 17875942) ; Biochem Biophys Res Commun. 2014 Jul 18;450(1):891-8. (PMID: 24971535) ; Trends Cell Biol. 2019 Apr;29(4):339-359. (PMID: 30691999) ; Vaccine. 2014 Feb 3;32(6):657-63. (PMID: 24333344) ; Biomolecules. 2019 Mar 15;9(3):. (PMID: 30884740) ; Front Immunol. 2018 Sep 07;9:2043. (PMID: 30245694) ; Immunology. 2009 Nov;128(3):311-23. (PMID: 20067531) ; Front Immunol. 2017 Sep 11;8:1083. (PMID: 28955330) Grant Information: P30 AI073961 United States AI NIAID NIH HHS; R01 AI108472 United States AI NIAID NIH HHS; R01 AI127347 United States AI NIAID NIH HHS Contributed Indexing: Keywords: Antigen specific B cells; Gene expression; H1N1; Influenza vaccination; PIK3C2B; Perinatally HIV infected children Substance Nomenclature: 0 (Antibodies, Viral) ; 0 (Influenza Vaccines) ; EC 2.7.1.137 (Class II Phosphatidylinositol 3-Kinases) ; EC 2.7.1.137 (PIK3C2B protein, human) Entry Date(s): Date Created: 20200425 Date Completed: 20210129 Latest Revision: 20211230 Update Code: 20231215 PubMed Central ID: PMC8714025

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Higher PIK3C2B gene expression of H1N1+ specific B-cells is associated with lower H1N1 immunogenicity after trivalent influenza vaccination in HIV infected children.