A phase 1 clinical trial testing an innovative vaccine method to prevent HIV has yielded promising results, IAVI and Scripps Research announced today. The vaccine has shown success in stimulating the production of rare immune cells needed to begin the process of generating antibodies against the fast-mutating virus; the targeted response was found in 97 percent of participants who received the vaccine.
This study presents a confirmation of a principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens, as well. With our many colleagues on the study team, we have shown that vaccines can be designed to stimulate rare immune cells with specific characteristics, and this targeted stimulation can be very effective in humans. We believe that this approach will be fundamental in the production of HIV vaccination and may be important in the immunization of other pathogens. “
William Schief, Ph.D., Professor and Immunologist, Scripps Research and Executive Director of Vaccine Design, IAVI Neutralization Center
Schief presented the findings on behalf of the research team at the International Society for HIV Research for Prevention (HIVR4P) inaugural conference today.
The study sets the stage for further clinical trials that seek to update and extend the approach – with the long-term goal of creating a safe and effective HIV vaccine. As a next step, IAVI and Scripps Research are partnering with biotechnology company Moderna to develop and test an mRNA-based vaccine that uses the approach to secrete the same beneficial immune cells. to implement. The use of mRNA technology could significantly accelerate the pace of HIV vaccine development.
HIV, which affects more than 38 million people worldwide, is known to be one of the most difficult viruses to target vaccines, largely because it is constantly evolving into different strains. to bypass the immune system.
“These exciting findings emerge from highly creative, innovative science and are a testament to the talent, commitment and collaborative spirit of the research team, and to the generosity of the experiment participants,” said Mark Feinberg, MD, Ph.D., president and CEO of IAVI. “Given the urgent need for HIV vaccination to enter the global disease, we believe these findings will have a far-reaching impact on those affected. -vaccination of HIV vaccines as they decide which scientific guidelines should be followed. The collaboration among individuals and institutions made this important and extremely complex. such a successful clinical trial will greatly accelerate the future uptake of HIV vaccination. “
One in a million
For decades now, HIV researchers have been working with the holy grail to stimulate the immune system to create rare but powerful antibodies that can neutralize different types of HIV. Known as “predominantly neoplastic antibodies,” or bnAbs, these specialized blood proteins may bind to HIV spikes, proteins on the surface of virion that allow the virus to enter your human cells, and the empowerment through important yet hard-to-reach areas that doesn’t change much from strain to strain.
“We and others announced many years ago that you need to start the process by stimulating bnAbs – cells that have specific properties that enable them to develop into bnAb secretory cells,” Schief explains. In this test, the target cells were only about one in a million B naïve cells. To get the correct antibody response, we first need to prime the right B cells. The data from this test confirm the ability of the immunogen vaccine to do this. “
The start-up phase was the first phase of a multi-step vaccination regimen that would aim to get many different types of bnAbs, he says.
A promise beyond HIV
The strategy for targeting naïve B cells with specific traits is called “germline target”, because these young B cells display antibodies encoded by undeveloped genes, or “germline”. “. Researchers believe the approach could be applied to vaccines for other resistant pathogens such as influenza virus, dengue, Zika, hepatitis C and malaria.
“This is a real achievement for vaccine science as a whole,” said Dennis Burton, Ph.D., professor and chair of the Department of Immunology and Microbiology at Scripps Research, scientific director of the IAVI Center for Antibody Neutralizing and director of the NIH Consortium for the Development of HIV / AIDS Vaccines. “This clinical trial has shown that we can direct immune responses in ways that are intended to produce new and improved vaccines, and not just for HIV. We believe that this type of vaccine engineering can be applied more widely, giving a new day in vaccination. “
The clinical trial, IAVI G001, was supported by IAVI and took place at two sites: George Washington University (GWU) in Washington, DC, and the Fred Hutchinson (Fred Hutch) Cancer Research Center in Seattle, enrolling 48 free- happy healthy adult. Participants received either a placebo or two doses of the vaccine, eOD-GT8 60mer, along with a supplement developed by the pharmaceutical company GSK. The lead investigators were Julie McElrath, MD, Ph.D., senior vice president and director of the Department of Vaccination and Infectious Diseases Fred Hutch, and David Diemert, MD, professor of medicine at GWU School of Medicine and Health Sciences. at the test sites.
“This is a unique study in the field of HIV vaccination, highlighting success in the first step of a pathway to promoting broad-spectrum neutral antibodies against HIV-1,” McElrath says. “The novel design of the immunogen, the clinical trial and the B-molecular cell analyzes provide a roadmap to accelerate further progress toward HIV vaccination.”
Extensive network of colleagues
Funding from the Bill & Melinda Gates Foundation, through the Collaboration for AIDS Vaccine Detection, supported a wide network of partners conducting complex analyzes.
The essential assay used to diagnose the vaccine candidate, epitope-specific single B cell classification and B cell receptor sequence (BCR), was developed and performed by teams at the NIH Vaccine Research Center, led by Adrian McDermott, Ph.D. (head of the immunization program), Richard Koup, MD (deputy director and head of the Department of Immunology and Psychology Laboratories), and research scientist David Leggat, Ph.D .; and by Fred Hutch, led by McElrath and senior scientist Kristen Cohen, Ph.D. Study design and data analysis were led by scientists Allan deCamp, Ph.D., Greg Finak, Ph.D., and Jimmy Fulp at Fred Hutch’s Center for Vaccine Statistics, with the help of Schief’s lab.
IAVI and Scripps Research developed the vaccine candidate with funding from the Bill & Melinda Gates Foundation, an HIV Vaccine Research and Development grant (P01 AI094419, entitled “Interacting HIV immunogen-BCR for vaccine development”) from the National Institute of Allergy and Infectious Diseases (NIAID), the Center for HIV / AIDS Vaccine Immunology and Immunogen Detection (CHAVI-ID) at NIAID and Scripps Research, and the Scripps Consortium for the Development of HIV / AIDS Vaccines (CHAVD). Other collaborative organizations include the Duke Human Vaccination Institute, the Karolinska Institute and the La Jolla Institute.
Research at the IAVI Neutralizing Antibody Center contributed to the development of the vaccine candidate, eOD-GT8 60mer, made possible by the Dutch government through the Minister of Foreign Trade & Cooperation Development and through the generous support of the American people through the Emergency Plan U.S. President for AIDS Relief (PEPFAR) through the United States International Development Agency (USAID). The content is the responsibility of IAVI and Scripps Research and does not necessarily reflect the views of USAID or the United States government.
Source:
Scripps Research Institute