Journal Article

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

Treanor, John, Barouch, Dan H., Abbink, Peter, Yallop, Christopher, Bunce, Catherine A., Neubauer, George H., Peter, Lauren, Frances, Doreen, Verlinde, Carl, Havenga, Menzo, Maxfield, Lori F., Park, Harriet, Lombardo, Angela, Nkolola, Joseph, Fast, Patricia, Keefer, Michael C., Lane, Christopher, Stephenson, Kathryn E.

2018

Overview

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. 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. 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. 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. ClinicalTrials.gov NCT02366013.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Acquired Immunodeficiency Syndrome - genetics / Acquired Immunodeficiency Syndrome - immunology / Acquired Immunodeficiency Syndrome - therapy / Acquired Immunodeficiency Syndrome - virology / Adenoviridae - genetics / Adenoviruses / Adult / Adults / AIDS / AIDS vaccines / AIDS Vaccines - genetics / AIDS Vaccines - immunology / AIDS Vaccines - therapeutic use / Analysis / Antigens / Antigens, Viral - genetics / Antigens, Viral - immunology / Antigens, Viral - therapeutic use / Attenuation / Biology and Life Sciences / Clinical trials / Dentistry / Disease transmission / Drug dosages / env Gene Products, Human Immunodeficiency Virus - genetics / env Gene Products, Human Immunodeficiency Virus - immunology / env Gene Products, Human Immunodeficiency Virus - therapeutic use / Enzyme-linked immunosorbent assay / Expression vectors / Female / Genetic Vectors - therapeutic use / Health care facilities / HIV / HIV infection / HIV-1 - genetics / HIV-1 - immunology / HIV-1 - pathogenicity / Human immunodeficiency virus / Humans / Immune response / Immune response (cell-mediated) / Immune response (humoral) / Immunity, Cellular - genetics / Immunity, Cellular - immunology / Immunogenicity / Infectious diseases / Male / Medicine / Medicine and Health Sciences / Middle Aged / Monkeys & apes / Mucosa / Prevention / Rectum / Replication / Research and Analysis Methods / Safety and security measures / Secretions / Shedding / Typhoid / Vaccines / Virology / Virus Replication - drug effects / Virus Replication - immunology / Viruses / Young Adult