First-in-human randomized controlled trial of an oral, replicating adenovirus 26 vector vaccine for HIV-1

PLoS One. 2018 Nov 14;13(11):e0205139. doi: 10.1371/journal.pone.0205139. eCollection 2018.


Background: Live, attenuated viral vectors that express HIV-1 antigens are being investigated as an approach to generating durable immune responses against HIV-1 in humans. We recently developed a replication-competent, highly attenuated Ad26 vector that expresses mosaic HIV-1 Env (rcAd26.MOS1.HIV-Env, "rcAd26"). Here we present the results of a first-in-human, placebo-controlled clinical trial to test the safety, immunogenicity and mucosal shedding of rcAd26 given orally.

Methods: Healthy adults were randomly assigned to receive a single oral dose of vaccine or placebo at 5:1 ratio in a dosage escalation of 10^8 to 10^11 rcAd26 VP (nominal doses) at University of Rochester Medical Center, Rochester, NY, USA. Participants were isolated and monitored for reactogenicity for 10 days post-vaccination, and adverse events were recorded up to day 112. Rectal and oropharyngeal secretions were evaluated for shedding of the vaccine. Humoral and cellular immune responses were measured. Household contacts were monitored for secondary vaccine transmission.

Results: We enrolled 22 participants and 11 household contacts between February 7 and June 24, 2015. 18 participants received one dose of HIV-1 vaccine and 4 participants received placebo. The vaccine caused only mild to moderate adverse events. No vaccine-related SAEs were observed. No infectious rcAd26 viral particles were detected in rectal or oropharyngeal secretions from any participant. Env-specific ELISA and ELISPOT responses were undetectable. No household contacts developed vaccine-induced HIV-1 seropositivity or vaccine-associated illness.

Conclusions: The highly attenuated rcAd26.MOS1.HIV-Env vaccine was well tolerated up to 10^11 VP in healthy, HIV-1-uninfected adults, though the single dose was poorly immunogenic suggesting the replicative capacity of the vector was too attenuated. There was no evidence of shedding of infectious virus or secondary vaccine transmission following the isolation period. These data suggest the use of less attenuated viral vectors in future studies of live, oral HIV-1 vaccines.

Trial registration: NCT02366013.

Publication types

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

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology
  • AIDS Vaccines / therapeutic use*
  • Acquired Immunodeficiency Syndrome / genetics
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / therapy*
  • Acquired Immunodeficiency Syndrome / virology
  • Adenoviridae / genetics
  • Adult
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Antigens, Viral / therapeutic use
  • Female
  • Genetic Vectors / therapeutic use
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity
  • Humans
  • Immunity, Cellular / genetics
  • Immunity, Cellular / immunology*
  • Male
  • Middle Aged
  • Virus Replication / drug effects
  • Virus Replication / immunology
  • Young Adult
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • env Gene Products, Human Immunodeficiency Virus / therapeutic use


  • AIDS Vaccines
  • Antigens, Viral
  • env Gene Products, Human Immunodeficiency Virus

Associated data

  • Dryad/10.5061/dryad.697r480