title: Immune reactivity after adenoviral-mediated aquaporin-1 cDNA transfer to human parotid glands.
abstract: OBJECTIVE
  The purpose of this study was to examine the humoral and cellular immune reactivity to adenoviral vector (AdhAQP1) administration in the human parotid gland over the first 42 days of a clinical gene therapy trial.
  
  
  METHODS
  Of eleven treated subjects, five were considered as positive responders (Baum et al, 2012). Herein, we measured serum neutralizing antibody titers, circulating cytotoxic lymphocytes, and lymphocyte proliferation in peripheral blood mononuclear cells. Additionally, after adenoviral vector stimulation of lymphocyte proliferation, we quantified secreted cytokine levels.
  
  
  RESULTS
  Responders showed little to modest immune reactivity during the first 42 days following gene transfer. Additionally, baseline serum neutralizing antibody titers to serotype 5-adenovirus generally were not predictive of a subject's response to parotid gland administration of AdhAQP1. Cytokine profiling from activated peripheral blood mononuclear cells could not distinguish responders and non-responders.
  
  
  CONCLUSIONS
  The data are the first to describe immune responses after adenoviral vector administration in a human parotid gland. Importantly, we found that modest (2-3 fold) changes in systemic cell-mediated immune reactivity did not preclude positive subject responses to gene transfer. However, changes beyond that level likely impeded the efficacy of gene transfer.
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.
authors.forename: I
authors.initials: I
authors.lastname: Alevizos
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Cotrim
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Goldsmith
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: McCullagh
authors.affiliation: Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, NC, USA.
authors.forename: T
authors.initials: T
authors.lastname: Berkowitz
authors.affiliation: Clinical Services Program, Leidos Biomedical Research, Inc, Frederick, MD, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Strobl
authors.affiliation: Clinical Services Program, Leidos Biomedical Research, Inc, Frederick, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Malyguine
authors.affiliation: Clinical Services Program, Leidos Biomedical Research, Inc, Frederick, MD, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Kopp
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Chiorini
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Nikolov
authors.affiliation: Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Neely
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.|Clinical Development, MedImmune, Gaithersburg, MD, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Illei
authors.affiliation: Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Baum
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood*; D051398:Aquaporin 1 / Q000235:genetics; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010306:Parotid Gland / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
chemical_list: C496020:AQP1 protein, human; D057134:Antibodies, Neutralizing; D016207:Cytokines; D018076:DNA, Complementary; D051398:Aquaporin 1
keywords: adenoviral; gene transfer; immune reactivity; parotid