mRNA vaccine candidates for HIV enter Phase I trial

The National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH), has begun a Phase I trial evaluating three experimental messenger RNA (mRNA) HIV vaccines. These vaccines are based on the same technology as the COVID-19 vaccines developed by Pfizer/BioNTech and Moderna.

The HVTN 302 trial (NCT05217641), sponsored by NIAID, is being conducted by NIAID-funded HIV Vaccine Trials Network (HVTN), based at Fred Hutchinson Cancer Research Center in Seattle, US.

“Finding an HIV vaccine has proven to be a daunting scientific challenge,” commented Dr Anthony Fauci, 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.”

mRNA vaccines deliver a segment of genetic material to human cells that instructs them to temporarily make a desired a protein fragment, eg, the surface protein of a virus, and express them on their surface. This enables the immune system to interact with the proteins and mount a substantial response if later exposed to that pathogen.

The HVTN 302 study will examine whether the following three experimental HIV mRNA vaccines are safe and can induce an immune response: 1) BG505 MD39.3 mRNA, 2) BG505 MD39.3 gp151 mRNA, and 3) BG505 MD39.3 gp151 CD4KO mRNA. Each investigational vaccine candidate is designed to present the Spike (S) protein found on the surface of HIV that facilitates entry into human cells. Each of the experimental vaccines encodes for different but highly related, stabilised proteins. None of the vaccine candidates can cause HIV infection.

News: NIH launches clinical trial of three mRNA HIV vaccines https://t.co/iXEtV3Xrpt

— NIH (@NIH) March 14, 2022

The specific mRNA sequences contained in the vaccines were designed and developed by investigators at the NIAID-funded 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, in collaboration with scientists at Moderna, Inc. Moderna manufactured the investigational vaccines through a NIAID-supported contract.

Led by principal investigators Dr Jesse Clark of the University of California Los Angeles and Dr Sharon Riddler of the University of Pittsburgh, the HVTN 302 study will enrol up to 108 adults ages 18 to 55 years at 11 sites in the US. 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 100µg 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 fulfilled, the remaining three groups of 18 participants each (Group B) will be vaccinated with 250µg of the assigned investigational vaccine, followed by injections two and six months after the initial vaccination. 

Safety and immune responses will be examined via blood and lymph node fine-needle aspiration samples taken at specified timepoints throughout the trial. Clinical staff will closely monitor participant safety throughout the study. The clinical trial is expected to be completed by July 2023.