The research, conducted at the Miller School’s Miami Center for AIDS Research, is being led by Geoffrey W. Stone, Ph.D., assistant professor of microbiology and immunology, and the results are published in the February 2014 issue of the Journal of Virology. The key finding is that the vaccine developed by Stone’s team, when targeted to a unique receptor in the immune system, can generate unprecedented T cell responses to HIV. The receptor involved is called CD40, and the vaccine uses a special form of its natural binding protein, CD40 ligand (CD40L), to enable important immune cells called dendritic cells to detect the presence of HIV proteins.
Dendritic cells are the gatekeepers of the immune system. They collect and process foreign proteins, known as antigens, and then alert the rest of the immune system to the invader. An essential step in this process is that the dendritic cells must become activated through the CD40 receptor.
Stone and his collaborators have found that directly coupling the foreign protein antigen to a special form of CD40 ligand leads to extraordinarily strong CD8+ T cell responses in mice. In the case of an HIV protein, the vaccinated mice were able to completely fend off infection by more than 10 million model viruses containing the HIV protein antigen. This type of extreme immune protection, called sterilizing immunity, is rarely seen in vaccine studies.
“The key to the vaccine’s effectiveness is that it contains a new form of CD40 ligand connected to the foreign protein antigen,” explained Stone. “This means that the dendritic cell both receives the antigen and is activated by its CD40 receptor at the same time.”
The research offers hope for the development of vaccines for other diseases, as well. Large numbers of CD8+ T cells can also protect against influenza, malaria and cancer, but no current vaccines generate enough CD8+ T cells to be effective.
“Vaccine-induced protection has been very difficult to achieve,” said Stone. “This new vaccine design takes us to another level in stimulating the immune system to produce CD8+ T cells. The next steps will be to test the vaccine in monkeys, and then in humans.”
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institute on Drug Abuse, both part of the National Institutes of Health, under award numbers K22AI068489, P30AI073961 and R43AI098246.
University of Miami