First Phase I trial of Ad26 vector begins
Dan Barouch and colleagues at the Beth Israel Deaconess Medical Center in Boston began enrolling volunteers in April for a Phase I clinical trial to evaluate the safety of an adenovirus serotype-26 (Ad26) vector-based vaccine candidate compared to an inactive placebo. The trial is being conducted at the Brigham and Women’s Hospital, also in Boston, and will involve 48 volunteers randomly assigned to receive either two or three doses of the vaccine candidate. The Ad26 vector is used to carry an HIV fragment in the hope that it will trigger immune responses against HIV. The vaccine candidate itself can not cause HIV infection.
There are several serotypes of adenovirus, which is one cause of the common cold, and AIDS vaccine candidates based on adenovirus serotype-5 (Ad5) have already been tested in clinical trials. Merck’s vaccine candidate, which was tested in the Phase IIb test-of-concept trial known as STEP, used an Ad5 vector, but this is the first time an Ad26-based vaccine candidate is being analyzed in human volunteers. Ad26 was chosen because fewer people are naturally exposed to this serotype of adenovirus and therefore levels of pre-existing immunity to Ad26 are much lower throughout the world. Pre-existing antibody immunity to the vaccine vector could potentially limit an individual’s immune responses against HIV.
In preclinical studies in nonhuman primates, Barouch and colleagues also found that the Ad26 vaccine candidate was more effective than an Ad5 candidate at protecting against infection with the monkey equivalent of HIV, known as simian immunodeficiency virus (SIV). This Ad26 vector “outperforms Ad5 vectors in rhesus macaques,” said Barouch. The vaccine candidate is manufactured by the Dutch biotechnology company, Crucell. —By Kristen Jill Kresge