IAVI Initiates Phase 1 Trial of Novel mRNA HIV Vaccine Targeting Broadly Neutralizing Antibodies
核心洞察
IAVI (搜索) launched the G004 Phase 1 clinical trial on December 15, 2025, testing three experimental HIV (搜索) vaccine immunogens delivered via Moderna's mRNA platform in 96 healthy participants across six South African sites.
The innovative vaccine strategy aims to coach the immune system to produce broadly neutralizing antibodies (bnAbs) that could provide protection against multiple HIV (搜索) strains, building on promising results from previous G001, G002, and G003 trials.
The dose escalation study will evaluate safety and immune responses while identifying the lowest effective dose, addressing skin reaction concerns observed in earlier trials.
IAVI (搜索) announced the initiation of its G004 Phase 1 clinical trial on December 15, 2025, marking a significant milestone in HIV (搜索) vaccine development. The first doses of experimental HIV vaccine antigens were administered at the Perinatal HIV Research Unit in Soweto, South Africa, launching a study that could advance the most promising HIV vaccine strategy to date.
Novel Vaccine Strategy Targets Broadly Neutralizing Antibodies
The IAVI (搜索) G004 trial is designed to test a groundbreaking hypothesis: that highly specialized vaccine immunogens, delivered in a specific sequence, can target certain B cells (搜索) within the immune system and coach them toward producing broadly neutralizing antibodies against HIV (搜索). Scientists widely believe that a vaccine inducing broadly neutralizing antibodies (bnAbs) could provide broad protection against many strains of HIV.
The study employs three immunogens developed by IAVI (搜索)/Scripps Research (搜索)—eOD-GT8 60mer, Core-g28v2 60mer (搜索), and N332-GT5 gp151 (搜索)—delivered on Moderna's mRNA platform. These immunogens were developed at Scripps Research in the laboratory of William Schief, Ph.D., professor at Scripps Research, vice president for protein design in infectious disease research at Moderna, Inc., and executive director of vaccine design at IAVI's Neutralizing Antibody Center.
"We are excited to evaluate these mRNA immunogens at lower doses, including two immunogens previously tested at higher doses and the first-in-human test of our N332-GT5 membrane-bound trimer aiming to prime a new type of bnAb," said Schief. "We are hoping this study will demonstrate safety and immunogenicity and lead to future studies that induce protective bnAbs."
Phase 1 Trial Design and Participant Population
The Phase 1 study will evaluate dose levels via a dose escalation model in 96 adult participants at six clinical sites across South Africa. All participants are healthy adults living without HIV (搜索). The model is specifically designed to identify the lowest dose of the immunogens that elicits an immune response while minimizing the risk of side effects, particularly skin reactions observed in the earlier completed IAVI (搜索) G002 study.
The clinical research centers conducting the trial include the Desmond Tutu Health Foundation (搜索) (DTHF) Emavundleni and Groote Schuur Hospital Clinical Research Sites in Cape Town, the eThekwini CAPRISA Research Clinic in Durban, the South African Medical Research Council (SAMRC) Isipingo Clinical Research Center in Isipingo Rail, the Setshaba Research Centre in Soshanguve, and the Perinatal HIV (搜索) Research Unit in Soweto.
Building on Promising Preclinical Results
IAVI (搜索) G004 builds on promising results observed in the IAVI G001, G002, and G003 clinical trials, which demonstrated proof of concept for a biological pathway to generate bnAbs against HIV (搜索). The trial will be conducted by African investigators who will also lead the detailed analysis of immune responses elicited by the immunogens.
"It is very exciting to see the launch of the IAVI (搜索) G004 clinical trial," said IAVI President and CEO Mark Feinberg, M.D., Ph.D. "With this year's global funding cuts to HIV (搜索) prevention, care, and treatment, bringing new prevention tools forward is more important than ever. We believe we are on the most promising path ever pursued for the development of an effective vaccine against HIV."
Addressing Critical Global Health Need
HIV (搜索) remains a significant global public health threat, with 40.8 million people living with HIV in 2024 and 1.3 million people newly acquiring HIV. New tools for HIV prevention remain a pressing public health need, and development of an efficacious and safe HIV vaccine that can deliver long-lasting immunity is an urgently sought public health goal.
Even with the advent of highly efficacious long-acting antiretroviral drugs for pre-exposure prophylaxis (PrEP), the availability of an efficacious HIV (搜索) vaccine will likely be required to sustainably control and eventually end the AIDS (搜索) pandemic.
Linda-Gail Bekker, MBChB, DTMH, DCH, FCP (SA), Ph.D., CEO of the Desmond Tutu Health Foundation (搜索), IAVI (搜索) Board of Directors member, and principal investigator for the study, emphasized the trial's significance: "Whilst there have been wonderful breakthroughs in pre-exposure prophylaxis in recent years, the need for a safe and effective vaccine to eliminate HIV (搜索) infection remains as urgent as ever. The commencement of this important trial in South Africa where that need is so great moves us closer to the goal of ending HIV for everyone everywhere."
Collaborative Funding and Development
Funding for this clinical trial has been provided by the Gates Foundation (搜索) through the Collaboration for AIDS (搜索) Vaccine Discovery (CAVD), with funding for clinical trial materials provided through the Scripps Research (搜索) Center for HIV (搜索)/AIDS Vaccine Development (CHAVD). Clinical trial materials were manufactured by Moderna, while IAVI (搜索) and Scripps Research scientists developed the vaccine candidate with Gates Foundation funding to the IAVI Neutralizing Antibody Center (NAC) under the CAVD. Additional research support came from the government of the Netherlands through the Minister of Foreign Trade & Development Cooperation.