Cape Town | A second large clinical trial to assess whether an experimental HIV vaccine regimen is safe, tolerable and able to prevent HIV infection is underway in the southern region of the African continent. This new Phase 2b proof-of-concept study, called Imbokodo, aims to enroll 2,600 HIV-negative women aged 18 to 35 years in sub-Saharan Africa and will be implemented at clinical trial sites through the National Institute of Allergy and Infectious Diseases (NIAID) funded HIV Vaccine Trials Network (HVTN).
Of 1.8 million new HIV infections worldwide in 2016, 43 percent occurred in eastern and southern Africa, with women and girls disproportionately affected. The first Imbokodo participants have received vaccinations at clinical research sites in South Africa, while regulatory processes are underway to conduct the study in Malawi, Mozambique, Zambia and Zimbabwe. With the start of Imbokodo, two HIV vaccine efficacy trials now are taking place in sub-Saharan Africa. Results from the ongoing Phase 2b/3 HVTN 702 study, which launched late last year and is enrolling HIV-negative men and women in South Africa, are expected in late 2020. Results from Imbokodo are expected in 2021.
The prime boost vaccine strategy being tested in Imbokodo includes utilizing “mosaic” immunogens – vaccine components inserted in an Adenovirus type 26 vaccine platform designed to induce immune responses against a wide variety of global HIV strains – combined with a protein vaccine boost. This regimen differs from the one being tested in HVTN 702. HVTN 702, an optimization of the moderately efficacious RV144 Thai trial, adapted to the clade C HIV epidemic of southern Africa: The Thai trial’s regimen is the only candidate HIV vaccine regimen ever shown to provide some protection against HIV.
“Both Imbokodo and HVTN 702 have resulted from years of scientific testing and clinical development, and they represent science’s current best efforts to develop a vaccine to prevent HIV infection,” said Kathy Mngadi, M.B.Ch.B., M.Phil., senior scientist at the Centre for the AIDS Programme of Research in South Africa (CAPRISA) and Imbokodo co-chair and site investigator. “We are grateful to the people of southern Africa who volunteer for these trials, and the communities in which the trials are conducted, to help develop what could be a true game-changer for the HIV/AIDS pandemic.”
“Ever since HIV was discovered 33 years ago, finding an effective HIV vaccine has been a top priority to help protect people at risk of infection. It’s a major scientific challenge, but today there is a new optimism that we can get there,” said Paul Stoffels, M.D., Chief Scientific Officer, Johnson & Johnson. “That’s why we’re joining forces with the world’s leading HIV researchers and global health advocates to help advance our experimental vaccine. Working together, our ultimate goal is to support efforts to make HIV history.”
In animal studies, regimens with mosaic-based vaccines protected monkeys against infection with an HIV-like virus. Findings from two early-stage human clinical trials suggest that these mosaic vaccines are well-tolerated and can generate anti-HIV immune responses in healthy adult volunteers. Based on results from an early-stage clinical trial called APPROACH, reported in July 2017, as well as early data from a second early-stage trial called TRAVERSE, researchers selected a lead candidate vaccine regimen for further evaluation.
"A safe and effective HIV vaccine will almost certainly be necessary to end the global HIV epidemic," said Dan Barouch, M.D., Ph.D., Professor of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, who led the early development of this vaccine.
Data from TRAVERSE confirmed the decision to move forward with the larger trial to evaluate whether the experimental regimen can prevent HIV infection. The ongoing TRAVERSE study is comparing two regimens containing vaccines that use a strain of common-cold virus engineered so that it does not cause illness (adenovirus serotype 26, or Ad26) to deliver either three (trivalent) or four (quadrivalent) mosaic immunogens among 198 healthy, HIV-negative adult volunteers in the United States and Rwanda. Interim data indicate that both are well-tolerated and can elicit anti-HIV immune responses. Imbokodo is evaluating the quadrivalent vaccine.
“We are in a golden age in HIV vaccine science. Currently we are exploring two different active HIV vaccine strategies as well as evaluating whether a trial using neutralizing antibodies can protect against HIV. In the next four years, we have the potential to change the game, and bring valuable tools to the public to protect communities from HIV”, said Professor Glenda Gray President & CEO of the South African Medical Research Council (SAMRC) and Protocol Chair of the Imbokodo study.
All Imbokodo participants will receive vaccinations at four time points over one year. They will be randomly assigned to receive either the experimental vaccine regimen or placebo. The experimental regimen comprises four doses of the quadrivalent mosaic vaccine. The final two doses will be given together with doses of an HIV protein, clade C gp140, and an aluminum phosphate adjuvant to boost immune responses. Participants will be followed for at least two years.
NOTES TO THE EDITOR
“Imbokodo,” the Zulu word for rock, is part of a well-known proverb in South Africa that refers to the strength of women and their importance in the community: Wathint’ abafazi, wathint’ imbokodo. You strike the women, you strike the rock.
The study is sponsored by Janssen Vaccines & Prevention, B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, with co-funding from two primary partners, the Bill & Melinda Gates Foundation and the U.S. National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID).
- The NIAID-funded HIV Vaccine Trials Network (HVTN), headquartered at Fred Hutchinson Cancer Research Center in Seattle, is implementing Imbokodo.
- The SAMRC provides both direct and indirect support to Imbokodo. The SAMRC will support the access to PrEP at the clinical trial sites, and is directly supporting the Mthatha clinical trial site. The SAMRC also supports community engagement at the trial sites and facilitates interests at the national and regional levels.
- Additional partners providing support include the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research, the U.S. Army Medical Materiel Development Activity, and the Ragon Institute of MGH, MIT and Harvard.
NIH. In Their Own Words… NIH Researchers Recall the Early Years of AIDS. Accessed November 2017. https://history.nih.gov/nihinownwords/docs/page_04.html; Nobel Prize. Press Release. 6 October 2008. www.nobelprize.org/nobel_prizes/medicine/laureates/2008/press.html
For comment from the U.S. National Institutes of Health, please email NIAIDnews@niaid.nih.gov.
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