title: Comparative Immunogenicity of HIV-1 gp140 Vaccine Delivered by Parenteral, and Mucosal Routes in Female Volunteers; MUCOVAC2, A Randomized Two Centre Study.
abstract: Defining optimal routes for induction of mucosal immunity represents an important research priority for the HIV-1 vaccine field. In particular, it remains unclear whether mucosal routes of immunization can improve mucosal immune responses.
  
  
  
  In this randomized two center phase I clinical trial we evaluated the systemic and mucosal immune response to a candidate HIV-1 Clade C CN54gp140 envelope glycoprotein vaccine administered by intramuscular (IM), intranasal (IN) and intravaginal (IVAG) routes of administration in HIV negative female volunteers. IM immunizations were co-administered with Glucopyranosyl Lipid Adjuvant (GLA), IN immunizations with 0.5% chitosan and IVAG immunizations were administered in an aqueous gel.
  
  
  
  Three IM immunizations of CN54 gp140 at either 20 or 100 μg elicited significantly greater systemic and mucosal antibodies than either IN or IVAG immunizations. Following additional intramuscular boosting we observed an anamnestic antibody response in nasally primed subjects. Modest neutralizing responses were detected against closely matched tier 1 clade C virus in the IM groups. Interestingly, the strongest CD4 T-cell responses were detected after IN and not IM immunization.
  
  
  
  These data show that parenteral immunization elicits systemic and mucosal antibodies in women. Interestingly IN immunization was an effective prime for IM boost, while IVAG administration had no detectable impact on systemic or mucosal responses despite IM priming.
  
  
  
  EudraCT 2010-019103-27 and the UK Clinical Research Network (UKCRN) Number 11679.
authors.affiliation: Centre for Infection, St George's, University of London, London, United Kingdom.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cosgrove
authors.affiliation: Hull York Medical School & Centre for Immunology and Infection, University of York, York, United Kingdom.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lacey
authors.affiliation: Mucosal Infection & Immunity Group, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Alethea V
authors.initials: AV
authors.lastname: Cope
authors.affiliation: Centre for Infection, St George's, University of London, London, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Bartolf
authors.affiliation: Hull York Medical School & Centre for Immunology and Infection, University of York, York, United Kingdom.
authors.forename: Georgina
authors.initials: G
authors.lastname: Morris
authors.affiliation: Mucosal Infection & Immunity Group, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Celine
authors.initials: C
authors.lastname: Yan
authors.affiliation: Centre for Infection, St George's, University of London, London, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Baden
authors.affiliation: Mucosal Infection & Immunity Group, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Cole
authors.affiliation: Infectious Disease Research Institute (IDRI), Seattle, WA, United States of America.
authors.forename: Darrick
authors.initials: D
authors.lastname: Carter
authors.affiliation: Medical Research Council, Clinical Trials Unit at UCL, University College London, London, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Brodnicki
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Medical Research Council, Clinical Trials Unit at UCL, University College London, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Joseph
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: DeRosa
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Lili
authors.initials: L
authors.lastname: Peng
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.|Department of Surgery, Duke University Medical Center, Durham, NC, United States of America.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: CAVD Neutralizing Antibody Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Mike
authors.initials: M
authors.lastname: Seaman
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.|Department of Surgery, Duke University Medical Center, Durham, NC, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.|Department of Surgery, Duke University Medical Center, Durham, NC, United States of America.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Medical Research Council, Clinical Trials Unit at UCL, University College London, London, United Kingdom.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stöhr
authors.affiliation: Medical Research Council, Clinical Trials Unit at UCL, University College London, London, United Kingdom.
authors.forename: Sheena
authors.initials: S
authors.lastname: McCormack
authors.affiliation: Mucosal Infection & Immunity Group, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D008875:Middle Aged; D009092:Mucous Membrane; D014621:Vagina; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D007074:Immunoglobulin G; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1