IAVI and Moderna have announced that first doses have been administered in a clinical trial of experimental HIV vaccine antigens at George Washington University (GWU) School of Medicine and Health Sciences in Washington, DC.
The Phase I trial, IAVI G002, is designed to test the hypothesis that sequential administration of priming and boosting HIV immunogens delivered by messenger RNA (mRNA) can induce specific classes of B-cell responses and guide their early maturation toward broadly neutralising antibody (bnAb) development.
The induction of bnAbs is widely considered to be a goal of HIV vaccination, and this is the first step in that process. The immunogens being tested in IAVI G002 were developed by scientific teams at IAVI and Scripps Research and will be delivered via Moderna’s mRNA technology.
“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform. The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine,” said Mark Feinberg, President and CEO of IAVI. “We are grateful to all of our partners and especially to the Bill & Melinda Gates Foundation for funding this trial.”
“We are very pleased to be partnering with IAVI and the Bill & Melinda Gates Foundation to apply our mRNA technology in the setting of HIV. At Moderna, we believe that mRNA offers a unique opportunity to address critical unmet public health needs around the world,” said Stephen Hoge, President of Moderna. “We believe advancing this HIV vaccine program in partnership with IAVI and Scripps Research is an important step in our mission to deliver on the potential for mRNA to improve human health.”
IAVI G002 is sponsored by IAVI and takes place at four sites: GWU School of Medicine and Health Sciences (lead investigator David Diemert), Hope Clinic of Emory Vaccine Center in Atlanta (lead investigator Srilatha Edupuganti), Fred Hutchinson Cancer Research Center (Fred Hutch) in Seattle (lead investigator Julie McElrath), and the University of Texas-Health Science Center at San Antonio (lead investigator Barbara Taylor).
The sites will enroll 56 healthy, HIV-negative adult volunteers. 48 participants will receive one or two doses of eOD-GT8 60mer mRNA Vaccine (mRNA-1644), with 32 of them receiving the boost Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core). An additional eight volunteers will receive the boost immunogen alone. Participants will be monitored for safety for six months after last vaccination. Participants’ immune responses to the vaccine candidates will be examined in molecular detail to evaluate whether the targeted responses were achieved.
The HIV vaccine antigens being evaluated as mRNA in this study were originally developed as proteins by William Schief, Professor at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center (NAC), and colleagues.
In 2021, Dr Schief announced results from the IAVI G001 clinical trial, showing that an adjuvanted protein-based version of the priming immunogen (eOD-GT8 60mer) induced the desired B-cell response in 97% of recipients.
IAVI G002 not only tests priming of the desired immune response using mRNA delivery of eOD-GT8 60mer, but also assesses the ability of a boosting immunogen to induce further maturation of B cells. Given the speed with which mRNA vaccines can be produced, this platform offers a more nimble and responsive approach to vaccine design and testing, potentially shaving off years from typical vaccine development timelines.
“We’ve seen promising proof of concept for germline targeting in IAVI G001, and this trial lets us take that approach to the next stage. What’s more, we’ve been able to expedite production of clinical trial material at a remarkably rapid pace because of Moderna’s technology,” said Schief.