The vaccine candidates, based on vectors made from adenovirus serotype 26 (Ad26) and adenovirus serotype 35 (Ad35), respectively, each contained synthetic versions of HIV’s envelope protein. The IAVI B003/IPCAVD-004/HVTN 091 Phase 1 clinical trial was a collaborative, multi-country study and the first to test these candidates in a prime-boost combination, in which different vaccine candidates are given sequentially to first prime and then boost immune responses. The study produced comparative data for six regimens in three regions, comparing different timing, order and combinations of the vaccine candidates. It enrolled 218 volunteers in Kenya, Rwanda, South Africa, and the United States.
Among the study’s findings:
- The vaccine regimens were all well tolerated with a good safety profile, and induced immune responses against HIV in all populations.
- A shorter (three-month) immunization schedule worked as well as a longer (six-month) schedule.
- Having antibodies to the adenovirus vectors from prior exposure did not significantly diminish the ability to make an immune response.
- Using just one vaccine twice gave a similar immune response to using two different vaccines.
- Some immune responses differed by geographic location.
The trial partners were IAVI; the Beth Israel Deaconess Medical Center (BIDMC); the HIV Vaccine Trials Network (HVTN); the National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS; the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; and Crucell Holland B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson. The Ragon Institute supported the U.S. trial site (Brigham and Women's Hospital in Boston); HVTN supported the South Africa sites (Desmond Tutu HIV Centre in Cape Town, Perinatal HIV Research Unit in Soweto and The Aurum Institute in Klerksdorp), and IAVI supported the East Africa sites, its Clinical Research Center partners in (Kenya AIDS Vaccine Initiative in Kangemi) and (Projet San Francisco in Kigali, Rwanda.)
This trial provided the first safety and immunogenicity data in Africa for the Ad26 vector, helping to make subsequent development possible.
The Janssen Pharmaceutical Companies of Johnson & Johnson are advancing a “heterologous prime-boost” vaccine regimen, which leverages AdVac® Technology from Janssen and a trimeric envelope protein boost, in collaboration with BIDMC, IAVI, NIAID, the Ragon Institute and the US Military HIV Research Program. Pre-clinical study results, published in the online edition of Science in July 2015, suggest that a “heterologous prime-boost” vaccine regimen could ultimately prove to be a strategy for protecting against HIV-1 infection. These data form the basis of vaccine regimens that are now being evaluated in an international Phase 1/2a clinical trial for safety and immunogenicity in healthy, HIV-uninfected volunteers with sites in the United States, Rwanda, South Africa, Uganda and Thailand.
Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention, Annals of Internal Medicine, 2 February 2016