Upfront
What's happening in HIV vaccine research?
by Chris Gadd
Twenty-five years into the AIDS pandemic there is still no preventive vaccine against HIV infection. However, research is continuing, and many important lessons have been learned along the way.
Three expert doctors from the United States recently summarised the state of play in HIV vaccine research in the scientific publication, Clinical Infectious Diseases. They explain that while HIV has thrown up a number of challenges to vaccine researchers, a number of studies that could lead the way to a vaccine in the future are planned or underway.
However, given the surprises and difficulties that this field has experienced over the past 20 years, the doctors stop short of estimating when a vaccine may become available.
Difficulties in HIV vaccine research
The doctors explain that the virus has three properties that have complicated the search for an effective vaccine. Firstly, after infection has taken hold, HIV hides its genetic material away within long-lived CD4 T-cells, ready to start producing more HIV particles at any time. This means that an effective HIV vaccine must be able to stimulate a long-lasting immune response to prevent new HIV production within the body.
Secondly, HIV damages the very immune cells (CD4 T-cells) that are needed for an effective vaccine; and thirdly, HIV is genetically diverse, with three main groups containing distinct subtypes, which are found at different proportions across the globe.
However, recent studies have begun to show more promise. Laboratory-produced ‘monoclonal’ antibodies (so-called, because they are derived from a single cell) that neutralise HIV's ability to attach to human cells can protect against a range of HIV strains in the test tube and have protected monkeys against infection with viruses related to HIV.
Vaccine design
HIV vaccine research has also been dogged by problems with traditional vaccine designs. Using live ‘attenuated’ (weakened) HIV-based vaccines is too dangerous due to the risk of HIV infection from the vaccine itself. Killed HIV vaccines do not produce an effective immune response. More success has been found using DNA-based vaccines to introduce HIV's genes into the body, often using other harmless viruses or bacteria (known as 'vectors') to carry the genes. Using a combination of more than one type of vaccine in a ‘prime and boost’ strategy may result in the best solution.
HIV vaccine vectors being developed at the moment include variations of the adenovirus (which causes the common cold). Two versions are in development, one by Merck and the other by the United States National Institutes of Health.
Cellular immunity
Recent research has also attempted to stimulate cellular immunity against HIV. This type of immunity is mediated by cell-killing CD8 T-cells or ‘cytotoxic T-lymphocytes’, which can identify and destroy cells that are infected with disease-causing organisms. However, cellular immunity is less likely to prevent HIV infection than antibody-mediated immunity.
Nevertheless, the development of a successful vaccine of this type could be used as well as, or in addition to, anti-HIV drugs in order to prevent the dramatic loss of CD4 T-cells soon after HIV infection, as well as reducing viral load after infection, resulting in slower disease progression and less chance of HIV being passed on.
Promise for the future?
Following successful safety trials, the Merck vaccine has already entered a large, long-lasting trial to determine its effectiveness, while the NIH vaccine is due to enter this phase next year, marking a new phase in vaccine research. It also hoped that the recent £155m boost to vaccine research internationally from the Gates Foundation might make a difference, although the International AIDS Vaccine Initiative estimate that closer to £650m a year is needed to really make a difference.