Biotechnology company Moderna, in association with The National Institute of Allergy and Infectious Diseases, has kicked off a Phase 1 human trial testing three different mRNA vaccine formulations designed to induce immunity against HIV. The trial is the second launched by Moderna this year to test mRNA vaccines for HIV.
“Finding an HIV vaccine has proven to be a daunting scientific challenge,” said NIAID director Anthony Fauci, in a statement announcing the Phase 1 trial. “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.”
The Phase 1 trial will enroll around 100 healthy adults, with the initial goal of evaluating the safety and immune responses to three different mRNA vaccine formulations. Each subject will receive three doses of their assigned mRNA formulation over a six-month period.
In the same way mRNA COVID-19 vaccines are designed to train the immune system to respond to the spike protein on the surface of SARS-CoV-2, these experimental vaccines focus on the HIV equivalent of the spike protein antigen target, known as an envelope glycoprotein trimer.
This protein on the surface of HIV particles is much more complex that the coronavirus spike protein, so Moderna has developed three different mRNA formulations to test, each encoding for a slightly different protein architecture.
The trial is expected to run until mid-2023. By that point it is hoped one of the three formulations will have demonstrated robust immune responses and Phase 2 trials can commence.
This Phase 1 trial is the second to commence this year involving Moderna and mRNA HIV vaccines. The first began in January and is testing an entirely different kind of mRNA vaccine.
This earlier Phase 1 trial is being run in collaboration with IAVI (the International AIDS Vaccine Initiative) and is testing a unique methodology designed to specifically target naive immune B cells and help induce them into the broadly neutralizing antibodies (bnAbs) known to target HIV.
This vaccine technique is called germline targeting. The Phase 1 trial is testing two different mRNA formulations, one designed as an antigen to prime the naive B cells, while the second dose uses a different antigen hoped to boost those cells into mature bnAbs.
This trial is also being conducted with healthy HIV-negative adults. Safety evaluation is the primary outcome but immune responses will also be measured over a 10-month follow up period. The trial will run until mid-2023.
Stephen Hodge, president of Moderna, said it has been challenging to induce immunity against HIV in the past using more traditional vaccine technologies, but he is optimistic mRNA could be an effective strategy.
“At Moderna we believe that mRNA offers and opportunity to take a fresh approach to this challenge,” Hodge said. “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.”
Over the last few months Moderna has dramatically expanded its mRNA vaccine research pipeline. Alongside these multiple HIV candidates it is now currently investigating mRNA vaccines targeting influenza, cytomegalovirus (CMV), the Epstein-Barr virus (EBV), the herpes simplex virus, the varicella-zoster virus, and a novel cancer vaccine.
