The new HIV vaccine has promising research into laboratory animals and human volunteers, pointing to potential ways to prevent lifelong viral diseases.
These experimental vaccines are built on mRNA technology, and in these early tests it causes several powerful immune responses and few side effects.
Scientists described the new vaccine in a pair of studies published Wednesday (July 30) in the journal Scientific Translation Medical. The first study tested several vaccines in rabbits and monkeys, and the promising results of that study led to further developments in Shot and subsequent human trials. The trial included over 100 healthy human volunteers and tested three vaccines similar to those tested in animals.
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“We’re talking about how we’re doing,” said Seth Cheetham, director of the Australian MRNA Cancer Vaccine Centre and associate director of the University of Queensland’s Basic mRNA Manufacturing Facility.
“Drugs for HIV treatment and prevention have changed the lives of people living with HIV, but effective vaccines are still urgently needed,” Cheetham, who was not involved in the job, told the Science Media Exchange.
According to the World Health Organization, the annual rate of new human immunodeficiency virus (HIV) infections has dropped significantly over the past decade, but hundreds of thousands still occur each year. Globally, an estimated 1.3 million people acquired HIV in 2024, including around 120,000 children. HIV vaccines can be converted in just a few quantities if they could boost the immune system’s ability to block the virus from colonizing at the first place.
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Currently, HIV prophylactics must be adopted continuously daily, other months or twice a year. This could pose certain challenges in areas with limited healthcare resources and infrastructure. Many scientists believe that vaccines will be key to ending the HIV/AIDS epidemic around the world. This is because such tools can effectively inhibit new infectious diseases and control the further spread of the disease.
However, creating an HIV vaccine is extremely difficult. The virus cleverly avoids the immune system by wearing a disguise, which mutates rapidly and constantly switches its appearance. Ideally, HIV vaccines will cause the production of elusive “widely neutralizing antibodies.” It is a protein that targets relatively invariant bits of viruses that are similar in many strains and may block infection, providing wide range of protection.
Scientists are exploring a variety of strategies to induce that protection. On that front, the researchers behind the new research have transformed into messenger RNA (mRNA), a molecule that functions as an indicator for cells to make proteins. They designed an experimental vaccine to carry the orientation of the protein complexes found on the surface of HIV. This complex, called “envelope trimers,” allows viruses to grab the surface of human immune cells and invade those cells.
Once injected into the body, the vaccine will encourage the cells to build one of the two versions of the envelope trimmer. One leaves the cell and floats, while the other remains tied to the surface of the cell. The free-floating version has been targeted in previous HIV vaccine studies, but previously did not produce appropriate neutralizing antibodies, the study authors noted.
They believe this is because on the surface of the actual HIV particles, the bottom of the trimer is embedded within the virus, and therefore hidden from view. They predicted that the latter version of the trimmer (which remains stuck to the cell) would cause a better neutralization response targeting the rest of the complex rather than the base.
It turned out to be true in both animal studies and early clinical trials.
For human trials, researchers recruited 108 healthy people, ages 18-55, split them into three groups, giving each group one of three mRNA vaccines. One vaccine encoded a free floating trimmer, with the latter two encoded boundary versions of different structures. Each participant received three doses of the assigned vaccine. One is the first visit, and the final dose after another 2 months and six months after the first visit.
Like animal testing, bound trimers elicited stronger signs of protection than free floating trimers. The bound trimmer vaccine produced neutralizing antibodies in 80% of vaccinated people, while the free-floating trimmer vaccine caused the same reaction in only 4% of recipients.
Related: 1st, HIV vaccine causes rare and elusive antibodies in humans
The bound trimmer vaccine also “generated a strong memory response, meaning that the body is better prepared to fight HIV for a long time after vaccination,” Cheetham noted. This is thanks to antibody-producing memory B cells. This lasts for a long time to build up a rapid immune response against the bacteria encountered in the past through infection or vaccination.
Human trials are primarily designed to look at vaccine safety, and “overall it was well tolerated.” They caused almost mild and temporary side effects, including fatigue, pain, headaches, chills, nausea, and pain at the injection site. However, the hive, also known as ur measles, was seen in seven participants, and the authors said it was “a much higher frequency than reported with the Covid-19 mRNA vaccine.” Several affected individuals experienced skin reactions for several months.
“Most side effects were mild and treatable, but some experienced skin reactions,” Cheetham said. “If next-generation versions reduce these side effects and the results continue in larger real-world studies in the community, mRNA vaccines could become a transformative tool in the fight against HIV.”
There were several other restrictions on the trial. First of all, it was open label. This means that researchers and vaccine recipients knew which shots were being given, which could bias the outcome. Furthermore, vaccines are not specifically designed to make widely neutralizing antibodies that can handle many strains, but rather to make neutralizing antibodies that can only tackle selected strains.
Nevertheless, the test results provide insight into the safety and efficacy of mRNA vaccines encoding the code for HIV envelope trimers, researchers noted. We will inform future efforts to improve these vaccines to induce a more broadly protective antibody response.
This article is for informational purposes only and is not intended to provide medical advice.
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