The story so far: Moderna, the Massachusetts-based US biotech company, said he could start human trials for an HIV (human immunodeficiency virus) vaccine in September, according to the ClinicalTrials.gov website, using the same mRNA platform that it used in its COVID-19 vaccine.
How should the vaccine candidate work?
Formally known as mRNA-1644, it is made in a way that stimulates the B cells of the immune system. These are a class of white blood cells that produce antibodies that can bind to invading bacteria and viruses. The broader purpose of stimulating B cells is to generate so-called broadly neutralizing antibodies (bnAbs), which are specialized blood proteins that bind to HIV surface proteins and deactivate them by accessing regions keys but difficult to access the virus. . Over the past decade, progress has been made in identifying new bnAbs from HIV-infected individuals that target very specific sites in the outer envelope of HIV. Laboratory analyzes and animal testing have improved understanding of how knowledge of these sites can be used to make immunogens (or parts of a virus or bacteria that elicit an antibody response from the system. (In the case of a coronavirus, for example, the spike protein is an immunogen against which different vaccines cause antibodies.)
One of these immunogens that was developed in the laboratory is eOD-GT8 60mer, developed by the International AIDS Vaccine Initiative (IAVI) and its partners. In a Phase I trial, scientists tested whether this approach would stimulate the human immune system to initiate the generation of bnAbs. Last February, IAVI announced that its trial had produced promising results and that its vaccine had been successful in stimulating the production of the bnAbs needed to stimulate antibodies. The targeted response was detected in 97% of participants. There were 48 healthy adults who volunteered for the trial, some of whom received the vaccine and some did not. The Moderna assay is designed to investigate a way to efficiently deliver the eOD-GT8 60mer immunogen using mRNA technology that will direct cells to make BnAbs that will trigger immune responses against HIV. For this trial, Moderna will recruit 56 healthy adults without HIV to test the vaccine’s 1644 mRNA safety and baseline immune response. Development of the vaccine involves funding from the Bill & Melinda Gates Foundation.
Why is this approach promising?
The quest to develop an HIV vaccine is considered the holy grail of scientific research. Although treatment with antiretroviral therapy has dramatically improved the longevity of people with AIDS, it is a lifelong treatment. According to the World Health Organization, an estimated 37.7 million people were living with HIV in 2020. Traditional vaccine approaches have not worked against HIV and, in fact, some of them have made the infection worse. . RNA-based immunogens are seen as a promising alternative because they do not involve the use of live virus, can be made relatively easily, can be deployed quickly, and administered safely. A disadvantage of mRNA vaccines was their instability. However, the experience with the coronavirus vaccine came like a bullet in the arm. The success of mRNA vaccines – Pfizer -BioNTech and Moderna – in reducing hospitalizations and mortality has led to confidence in the underlying platform and, therefore, new investments to improve it.
What are the challenges ahead?
Of people living with HIV, more than two-thirds are in Africa. Any success in bringing the HIV pandemic under control would mean a drastic reduction in transmission rates there. However, as experience with Moderna and Pfizer vaccines shows, getting essential jabs in areas where they are needed most is the biggest stumbling block. Another challenge with mRNA vaccines is that they are temperature sensitive in storage, and present a challenge for developing countries. HIV has mutated into several variants and is an insidious virus, and it will be many years before definitive proof of the success of the mRNA approach can be established.