The US trial will evaluate the safety and immunogenicity of three candidates, also exploring different dose levels.
It represents the second HIV vaccine trial initiated by Moderna this year, with another Phase 1 trial already under way to test HIV vaccine antigens.
Leveraging the power of mRNA
The new HIV trimer mRNA vaccine trial is assessing three candidates: BG505 MD39.3 mRNA; BG505 MD39.3 gp151 mRNA; and BG505 MD39.3 gp151 CD4KO mRNA.
As with the mRNA tech used with COVID-19 vaccines, the candidates work by delivering a piece of genetic material that instruct the body to make a protein fragment of the target pathogen. The immune system then mounts a response against the pathogen, thus becoming prepared for future exposure.
Each investigational vaccine candidate is designed to present the spike protein found on the surface of HIV that facilitates entry into human cells. Each of the experimental vaccines encodes for different but highly related, stabilized proteins. None of the three vaccine candidates can cause HIV infection.
The specific mRNA sequences contained in the vaccines were designed and developed by investigators at the Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD) at the Scripps Research Institute and the Bill & Melinda Gates Foundation-funded IAVI Neutralizing Antibody Center at Scripps. Moderna manufactured the investigational vaccines through a NIAID-supported contract.
The primary hypothesis is that the soluble and membrane-bound HIV envelope trimer mRNA vaccines will be safe and well-tolerated by HIV-uninfected individuals and will elicit autologous neutralizing antibodies.
"Developing a vaccine regimen that induces sustained protective levels of HIV neutralizing antibodies in humans has been difficult to achieve. At Moderna, we believe that mRNA offers an opportunity to take a fresh approach to this challenge. With the launch of our second HIV vaccine trial, we are advancing our strategy to utilize multiple mRNA encoded native-like HIV trimers and leverage the power of our mRNA platform to accelerate the discovery of a protective HIV vaccine," said Stephen Hoge, M.D., president of Moderna.
HIV is the virus responsible for acquired immunodeficiency syndrome (AIDS). Worldwide, approximately 38 million are currently living with HIV, including approximately 1.2 million in the US.
Phase 1 study
A total of 108 healthy, HIV-uninfected adults (aged 18-55 years old) will take place in the open-label, multicenter, randomized phase 1 study will evaluate the safety and immunogenicity of three candidates. Doses of 100 mcg or 250mcg will be administered via intramuscular (IM) injections into the deltoid muscle. A dose escalation plan will be implemented in the low-dose groups.
The NIAD, part of the National Institutes of Health, is sponsoring the study, called HVTN 302. The NIAID-funded HIV Vaccine Trials Network (HVTN), based at Fred Hutchinson Cancer Research Center in Seattle, is conducting the trial. The study is set to run until June 2023.
“Finding an HIV vaccine has proven to be a daunting scientific challenge,” said Anthony S. Fauci, M.D. NIAID director. “With the success of safe and highly effective COVID-19 vaccines, we have an exciting opportunity to learn whether mRNA technology can achieve similar results against HIV infection.”
Led by principal investigators Jesse Clark, M.D., of the University of California Los Angeles, and Sharon Riddler, M.D., of the University of Pittsburgh, the HVTN 302 study will cover 11 sites: Birmingham, Alabama; Boston; Los Angeles; New York City; Philadelphia; Pittsburgh; Rochester, New York and Seattle.
Each participant will be randomly assigned to one of six groups each receiving three vaccinations of one of the experimental vaccines. The first three groups (18 participants each), called Group A, will receive intramuscular injections of 100 micrograms (mcg) of their assigned vaccine candidate at the initial visit, at month two and again at month six. Participants in Group A will be evaluated two weeks after initial vaccination to ensure safety criteria have been met. If so, the remaining three groups of 18 participants each (Group B) will be vaccinated with 250 mcg of the assigned investigational vaccine, followed by injections two and six months after the initial vaccination.
Other HIV vaccine work
In addition to this HIV trimer mRNA vaccine trial of mRNA-1574, Moderna is partnering in testing of HIV vaccine antigens mRNA-1644 and mRNA-1644v2-Core, being evaluated in a Phase 1 trial sponsored by IAVI and supported by the Bill & Melinda Gates Foundation.
Launched in January, this 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 neutralizing 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.
