The story so far: Moderna, the Massachusetts-based American biotechnology company, has indicated that it may begin human trials for a vaccine for HIV (human immunodeficiency virus) in September , according to the ClinicalTrials.gov website, employing the same m-RNA platform that it has used in its COVID-19 vaccine.
How is the candidate vaccine expected to work?
Formally known as mRNA-1644, it is made in a way to stimulate the B cells of the immune system. These are a class of white blood cells that produce antibodies which can bind to invading bacteria and viruses. The larger purpose of stimulating the B cells is to generate what are called broadly neutralising antibodies (bnAbs), which are specialised blood proteins that attach to the surface proteins of HIV and disable them by accessing key but hard-to-reach regions on the virus. Over the last decade, there have been advances in identifying new bnAbs from HIV-infected individuals that were seen to target very specific sites in the outer envelope of the HIV. Lab-based analysis and tests on animals have improved the understanding of how the knowledge of these sites can be used to make immunogens (or parts of a virus or bacteria that elicit an antibody response from the immune system. In the case of a coronavirus, for instance, the spike protein is an immunogen against which different vaccines elicit antibodies.)
One such immunogen that has been designed in the lab 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. This February, IAVI announced that their trial produced promising results and their vaccine had succeeded in stimulating the production of the bnAbs needed to stimulate antibodies. The targeted response was detected in 97% of the participants. There were 48 healthy adults who had volunteered in the trial, some of whom got the vaccine and some did not. The Moderna trial is designed to investigate a way to effectively deliver the eOD-GT8 60mer immunogen using the m-RNA technology that will direct cells to make the BnAbs which will elicit immune responses against HIV. For this trial, Moderna will recruit 56 healthy adults without HIV to test the safety of the vaccine mRNA-1644 and basic immune response. The vaccine’s development involves funding from the Bill & Melinda Gates Foundation.
Why is this approach promising?
The quest to develop an HIV vaccine is considered among the holy grails of scientific research. While treatment with Anti-Retroviral Therapy has significantly improved the longevity of those with AIDS, this is a lifelong treatment. According to the World Health Organization, there are around 37.7 million living with HIV as of 2020. Traditional vaccine approaches have not worked for HIV, and in fact, some of them have gone on to worsen infection. RNA-based immunogens are believed to be a promising alternative because they do not involve the use of a live virus, can be made relatively easily, can be quickly deployed and safely administered. A drawback of m-RNA vaccines used to be their instability. However, the experience with the coronavirus vaccine has come as a shot in the arm. The success of m-RNA vaccines — Pfizer -BioNTech and Moderna — in reducing hospitalisation and mortality has led to confidence in the underlying platform and, therefore, fresh investments to improve it.
What are the challenges ahead?
Of the people living with HIV, over two-thirds are in Africa. Any success in containing the HIV pandemic would mean drastically cutting the rates of transmission there. However, as the experience with the Moderna and Pfizer vaccines shows, getting essential jabs to the regions where they are most needed is the biggest stumbling block. Another challenge with m-RNA vaccines is that they are sensitive to temperature in storage, and is 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 m-RNA approach can be established.