Researchers at the Texas Biomedical Research Institute are developing a vaccine candidate against HIV. The vaccine is intended to block HIV entry into the body and is administered to the mucosal lining of the rectum and vagina to achieve this. The formulation then stimulates antibodies against HIV in precisely the areas where the virus first enters the body’s cells. Cleverly, the researchers designed the vaccine to target the basal cells of the epithelium, which then give rise to a constant supply of epithelial cells to replace cells that are routinely sloughed off. This may lead to long-term protection against HIV with this vaccine. In tests with primates, the vaccine has shown significant efficacy in reducing viral transmission, and when vaccinated animals did become infected, they were able to control the infection much better and showed no disease symptoms.
HIV has evaded our best attempts to create an effective vaccine for decades. Although anti-retroviral therapy can allow people with HIV infection to live normal lives and avoid progression to AIDS, it still requires that someone takes these treatments for the rest of their lives. Moreover, these treatments may not be widely available for everyone, and lack of access can be an issue in low-resource areas. A vaccine that prevents people from getting infected with HIV in the first place, and allows them to control the infection if it does occur, would be very useful.
A microscopy image of vaginal tissue from a female macaque vaccinated with a version of the vaccine. The white line is the basal or base layer of the mucosal epithelium, which is the interior tissue lining; cells stained in blue have built up along the lining through the menses cycle; and cells glowing green contain the vaccine, forming the top layer of the lining, which pathogens would encounter first.
Part of the issue is that HIV spreads through the body relatively quickly. In response, these researchers had the idea of developing a vaccine that acts specifically on the areas of the body where the virus typically enters – the mucosal lining of the vagina or rectum. The concept is to give the virus a hard time before it even gets a chance to get a foothold in the body. “I had this idea as a postdoc,” said Marie-Claire Gauduin, a researcher involved in the study. “I thought it had to be naïve because nobody was talking about it. It was so obvious and simple to me; I thought someone would have already done it.”
The vaccine is a live attenuated vaccine, meaning that the viral particles within contain the full genetic code, albeit with some alterations to prevent the virus from replicating. The researchers describe the resulting particles as “single-cycle” vaccine virus. These modified viral particles can enter cells in the mucosa, but cannot proliferate and leave the cells again. The immune system can recognize that these cells are ‘infected’ and so generates antibodies against the virus, which will give any real virus attempting to enter the mucosa a hard time.
Cleverly, the vaccine targets cells in the mucosa that give rise to new cells, helping to keep the vaccine effective for as long as possible. “The idea is that as long as the vaccine is in the mother cells, it will be passed on and be present in all new epithelial cells in these regions,” said Gauduin. “I didn’t think it would work so well, but it did!”
In tests in non-human primates, the vaccine candidate helped animals to avoid infection in the first place, and once infected they showed a better ability to control the virus and showed no disease symptoms. It’s too early to know if the vaccine will work in humans, but the researchers have recently received some funding to develop it further.
