HVTN 100 Clinical Trial Findings Advance HIV Vaccine Research and Development

SEATTLE — June 26, 2018

An HIV vaccine regimen tested in an early-phase clinical trial elicited robust immune responses that appeared to be stronger than those observed in a landmark 2009 study showing that a vaccine can protect people from HIV infection.  These findings from the ongoing Phase I/II HVTN 100 study were published on June 10 in Lancet HIV.

The trial studied a vaccine regimen designed to improve upon the one used in the 2009 study, the U.S. Military HIV Research Program-led RV144 trial in Thailand, the only study to-date to show protection, albeit modest, in humans.  To build on the RV144 findings, the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health and the NIAID-funded HIV Vaccines Trials Network (HVTN) joined with other organizations to form the Pox-Protein Public-Private Partnership (P5), a public-private collaboration, to improve upon the potency, breadth and duration of protection seen in RV144. The early results from HVTN 100 show stronger immune responses than some of those recorded in RV144, suggesting the potential for higher levels of protection from the modified vaccine regimen.

The vaccine regimen administered in the HVTN 100 trial is based on the RV144 regimen but designed to elicit immune responses to the HIV subtype common in sub-Saharan Africa. In addition, the adjuvant was changed in an effort to improve the immune response to the regimen.  Also, an additional vaccination was included at one year in the HVTN 100 trial in an effort to prolong the early protective effect observed in RV144.

The trial was chaired by two South African researchers, Professor Linda-Gail Bekker, HVTN 100 Protocol Chair and Dr Fatima Laher, HVTN 100 Co-chair. They collaborated with six South African trial centers to enroll HIV-negative adult volunteers starting in February 2015. Of the 252 people enrolled in the study, 210 received the vaccine regimen and 42 received a salt-water placebo. The researchers followed the volunteers over the years to better understand the immune response to the vaccine.

“These early-phase trial results show promise. There was a pre-specified set of immune response criteria to signal whether the regimen should move forward into advanced phase testing or not. Those criteria were met, which is why we are currently conducting HVTN 702, an advanced-phase large-scale trial that seeks to understand if the vaccines can prevent HIV infection in human beings,” explains Bekker, HVTN 100 Protocol Chair.

Results from HVTN 100 showed that all volunteers who completed the first four vaccinations developed antibody responses two weeks after the fourth vaccination. Similarly, cellular immune responses were strong.

The South African Medical Research Council (SAMRC), one of the partners involved in the study, funded aspects of the immunological studies that were conducted in South Africa.  “South Africa is committed to finding a biomedical intervention to prevent HIV transmission. An effective HIV vaccine will be the instrument required to curtail this epidemic,” says Professor Glenda Gray, President and CEO of the SAMRC.

The HVTN 100 story continues to unfold

“We now know that the vaccine regimen in HVTN 100 can produce strong immune responses early on, but there remains the question of immune durability: Will vaccine-induced immune responses last over time if a fifth vaccination time point is added?” says Laher, HVTN 100 Co-chair.

The research team is planning to conclude the HVTN 100 trial this year, and will next report on continued safety, durability, breadth and function of immune responses, and the effects of subsequent boosting vaccinations.

“The recent progress in the development of new tools to map the human immune response to vaccination is exciting.  The depth of immunity elicited in the HVTN 100 trial is only just beginning to be uncovered. The continued insights from HVTN 100, together with HVTN 702, will provide an opportunity to reveal a full picture of protective immunity,” says Georgia Tomaras, Principal Investigator at the HVTN Laboratory.

“The MF59 adjuvant utilized in HVTN 100 was selected because it enhanced the potency, durability and effectiveness of influenza vaccines as compared to more commonly used adjuvants such as alum.  Potency was enhanced by this adjuvant in the HVTN 100 vaccine regimen,” says Larry Corey, M.D., Principal Investigator of the HVTN, virologist and faculty member at Fred Hutchinson Cancer Research Center.

HVTN 100 and HVTN 702 are part of a larger HIV vaccine research endeavor led by the Pox-Protein Public-Private Partnership, or P5—a diverse group of public and private organizations committed to building on the success of the RV144 trial. The P5 aims to produce an HIV vaccine that could have a significant public health benefit in southern Africa and to advance scientists’ understanding of the immune responses associated with preventing HIV infection. P5 members include NIAID, the Bill & Melinda Gates Foundation, the South African Medical Research Council, HVTN, Sanofi Pasteur, GSK and the U.S. Military HIV Research Program.

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Access to manuscript:
https://www.ncbi.nlm.nih.gov/pubmed/29898870

Funding: 
US National Institute of Allergy and Infectious Diseases (NIAID), and Bill & Melinda Gates Foundation.

Authors: 
Linda-Gail Bekker, Zoe Moodie, Nicole Grunenberg, Fatima Laher, Georgia D Tomaras, Kristen W Cohen, Mary Allen, Mookho Malahleha, Kathryn Mngadi, Brodie Daniels, Craig Innes, Carter Bentley, Nicole Frahm, Daryl E Morris, Lynn Morris, Nonhlanhla N Mkhize, David C Montefiori, Marcella Sarzotti-Kelsoe, Shannon Grant, Chenchen Yu, Vijay L Mehra, Michael N Pensiero, Sanjay Phogat, Carlos A DiazGranados, Susan W Barnett, Niranjan Kanesa-thasan, Marguerite Koutsoukos, Nelson L Michael, Merlin L Robb, James G Kublin, Peter B Gilbert, Lawrence Corey, Glenda E Gray, M Juliana McElrath, on behalf of the HVTN 100 Protocol Team*

About Fred Hutchinson Cancer Research Center
At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first National Cancer Institute-funded cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network.

CONTACT
Media Relations
Aziel Gangerdine
HVTN: Director of Communications
C 206.384.0945 / O 206.667.7875
agangerd@fredhutch.org