title: Differential blood and mucosal immune responses against an HIV-1 vaccine administered via inguinal or deltoid injection.
abstract: Mucosal immunity is central to sexual transmission and overall pathogenesis of HIV-1 infection, but the ability of vaccines to induce immune responses in mucosal tissue compartments is poorly defined. Because macaque vaccine studies suggest that inguinal (versus limb) vaccination may better target sexually-exposed mucosa, we performed a randomized, double-blinded, placebo-controlled Phase I trial in HIV-1-uninfected volunteers, using the recombinant Canarypox (CP) vaccine vCP205 delivered by different routes. 12 persons received vaccine and 6 received placebo, divided evenly between deltoid-intramuscular (deltoid-IM) or inguinal-subcutaneous (inguinal-SC) injection routes. The most significant safety events were injection site reactions (Grade 3) in one inguinal vaccinee. CP-specific antibodies were detected in the blood of all 12 vaccinees by Day 24, while HIV-1-specific antibodies were observed in the blood and gut mucosa of 1/9 and 4/9 evaluated vaccinees respectively, with gut antibodies appearing earlier in inguinal vaccinees (24-180 versus 180-365 days). HIV-1-specific CD8(+) T lymphocytes (CTLs) were observed in 7/12 vaccinees, and blood and gut targeting were distinct. Within blood, both deltoid and inguinal responders had detectable CTL responses by 17-24 days; inguinal responders had early responses (within 10 days) while deltoid responders had later responses (24-180 days) in gut mucosa. Our results demonstrate relative safety of inguinal vaccination and qualitative or quantitative compartmentalization of immune responses between blood and gut mucosa, and highlight the importance of not only evaluating early blood responses to HIV-1 vaccines but also mucosal responses over time.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00076817.
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; AIDS Healthcare Foundation, Los Angeles, California, United States of America.
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Ibarrondo
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Price
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Lance E
authors.initials: LE
authors.lastname: Hultin
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Elliott
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Hultin
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Roger
authors.initials: R
authors.lastname: Shih
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Hausner
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Hwee L
authors.initials: HL
authors.lastname: Ng
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hoffman
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Jamieson
authors.affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Anton
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use*; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D028121:Canarypox virus; D057645:Deltoid Muscle; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1; D006801:Humans; D056724:Immunity, Humoral; D018928:Immunity, Mucosal / Q000276:immunology*; D007264:Inguinal Canal; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D016915:AIDS Vaccines; C000594377:ALVAC-HIV vCP205 vaccine; D015483:HIV Antibodies; D014614:Vaccines, Synthetic