MASSACHUSETTS, United States – American pharmaceutical and biotechnology company Moderna began trials of its experimental mRNA vaccine against HIV last Wednesday.
Moderna recruited 56 healthy, HIV-negative adults to test the safety of the mRNA-1644 vaccine and baseline immune response.
The vaccine is a collaboration between Moderna, the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation (BMGF).
The candidate, mRNA-1644, is based on the same mRNA platform as Moderna’s high-potency Covid-19 syringe, which is one of two of the few approved mRNA vaccines in the world.
The other is Pfizer-BioNTech’s Covid-19 vaccine. “A particularly challenging year for the company as a whole, 2020 has proven to be an exceptional proof-of-concept period for Moderna,” Moderna CEO Stephane Bancel said in a January 2021 program update. company vaccines.
“Although we have shown that our mRNA-based vaccine can prevent Covid-19, this has encouraged us to pursue more ambitious development programs as part of our prophylactic vaccine modality. Today we are announcing three new vaccination programs for seasonal influenza, HIV and Nipah virus, some of which have escaped traditional vaccination efforts and which we believe can all be addressed with our mRNA technology.
mRNA-1644 is the first HIV mRNA vaccine to be tested in humans. Moderna will also test another version of the candidate called mRNA-1644v2 core. Both have been tested for safety on non-human subjects.
Targeting B-cell Responses
mRNA-1644 is designed to stimulate B cells of the immune system to produce broadly neutralizing antibodies (bnAbs) against the virus.
In 2009, previously undescribed potent bnAbs were identified for the first time from large groups of HIV-infected individuals.
It was the isolation of these antibodies that reignited activity in the development of an HIV vaccine. By studying how these antibodies interact with the virus and neutralize it in laboratory tests, scientists have been able to highlight many weaknesses of the HIV virus, which they have used to develop immunogenic vaccines.
The first of these modified immunogens is eOD-GT8 60mer developed by IAVI and its partners.
In a phase I study, scientists tested whether this approach would stimulate the human immune system to initiate the production of bnAbs.
Another development that has sparked interest in designing immunogens to induce bnAbs has been a better understanding of HIV’s outermost protein – the HIV envelope glycoprotein, which is the target of all bnAbs.
“For decades, scientists have been hampered by their inability to determine the precise structure of this notoriously unstable trimeric protein,” IAVI noted.
“But recent advances have allowed them to both stabilize and understand the HIV envelope in unprecedented detail.”
Now, Moderna’s study will look at how the eOD-GT8 60mer immunogen can be delivered using Moderna’s mRNA technology and investigate how mRNA can be used to prompt cells to make proteins that stimulate immune responses against HIV.
The Holy Grail For HIV On The Horizon?
HIV is a highly stigmatized virus that is no longer a death sentence but is responsible for acquired immunodeficiency syndrome (AIDS), a progressive and lifelong disease without effective treatment.
According to Moderna, approximately 38 million people are currently living with HIV worldwide, including 1.2 million in the United States.
Approximately two million new HIV infections are acquired worldwide each year and approximately 690,000 people die of HIV/AIDS each year.
The most common routes of transmission are sexual intercourse and intravenous drug use, which means young people are most at risk of infection.
HIV represents a significant economic burden – from 2000 to 2015, a total of US$562.6 billion was spent globally on HIV care, treatment and prevention.
The first vaccine against this devastating disease is considered the holy grail of pharmacy.
There have already been several attempts, but many have been uncertain and most have shown no evidence of efficacy – two studies evaluating adenovirus type 5 (Ad5) vectored HIV vaccines in the 2000s have in increases the risk of HIV infection.
(This article was originally published by Clinical Trials Arena)