title: Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans.
abstract: BACKGROUND
  Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans.
  
  
  METHODS
  In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed.
  
  
  RESULTS
  Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry.
  
  
  CONCLUSIONS
  These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation.
  
  
  BACKGROUND
  NCT01103687.
authors.affiliation: Brigham and Women's Hospital Beth Israel Deaconess Medical Center Harvard Medical School Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.affiliation: Beth Israel Deaconess Medical Center Harvard Medical School.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beth Israel Deaconess Medical Center Harvard Medical School.
authors.forename: Hualin
authors.initials: H
authors.lastname: Li
authors.affiliation: Brigham and Women's Hospital Harvard Medical School.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Brigham and Women's Hospital Beth Israel Deaconess Medical Center Harvard Medical School.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Walsh
authors.affiliation: Brigham and Women's Hospital.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Kleinjan
authors.affiliation: Brigham and Women's Hospital.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Engelson
authors.affiliation: Beth Israel Deaconess Medical Center Harvard Medical School.
authors.forename: Lauren
authors.initials: L
authors.lastname: Peter
authors.affiliation: Beth Israel Deaconess Medical Center Harvard Medical School.
authors.forename: Peter
authors.initials: P
authors.lastname: Abbink
authors.affiliation: Brigham and Women's Hospital Harvard Medical School.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Milner
authors.affiliation: Brigham and Women's Hospital Harvard Medical School.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Golden
authors.affiliation: Brigham and Women's Hospital Harvard Medical School.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Viani
authors.affiliation: Brigham and Women's Hospital Harvard Medical School.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Stachler
authors.affiliation: Brigham and Women's Hospital Harvard Medical School.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Chen
authors.affiliation: Crucell Holland BV, Leiden, The Netherlands.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Pau
authors.affiliation: Crucell Holland BV, Leiden, The Netherlands.
authors.forename: Mo
authors.initials: M
authors.lastname: Weijtens
authors.affiliation: Beth Israel Deaconess Medical Center.
authors.forename: Brittany R
authors.initials: BR
authors.lastname: Carey
authors.affiliation: Beth Israel Deaconess Medical Center.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Miller
authors.affiliation: Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Swann
authors.affiliation: EMMES Corporation, Rockville.
authors.forename: Mark
authors.initials: M
authors.lastname: Wolff
authors.affiliation: EMMES Corporation, Rockville.
authors.forename: Hayley
authors.initials: H
authors.lastname: Loblein
authors.affiliation: Beth Israel Deaconess Medical Center Harvard Medical School Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Brigham and Women's Hospital Beth Israel Deaconess Medical Center Harvard Medical School Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston.
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
authors.affiliation: Beth Israel Deaconess Medical Center Harvard Medical School Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000260:Adenoviruses, Human / Q000276:immunology*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007273:Injections, Intramuscular; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: HIV; adenovirus; mucosal immunity; vaccine