Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans

J Infect Dis. 2015 Feb 15;211(4):518-28. doi: 10.1093/infdis/jiu485. Epub 2014 Aug 26.

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.

Clinical trials registration: NCT01103687.

Keywords: HIV; adenovirus; mucosal immunity; vaccine.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / adverse effects
  • AIDS Vaccines / immunology*
  • Adenoviruses, Human / immunology*
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • Colon / immunology
  • Colon / pathology
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Antibodies / blood
  • HIV Antibodies / immunology
  • HIV Infections / prevention & control
  • HIV-1 / immunology*
  • Humans
  • Immunity, Mucosal / immunology*
  • Injections, Intramuscular
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Young Adult
  • env Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • Cytokines
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus

Associated data

  • ClinicalTrials.gov/NCT01103687