A vaccine that produces broadly neutralizing antibodies against different HIV subtypes in monkeys is reported this week in a paper in the Proceedings of the National Academy of Sciences. As first made public last September at the annual meeting of Dr Robert Gallo’s Institute of Human Virology (IHV) in Baltimore, Maryland, this is based on fusing a human protein – the CD4 molecule – with part of the HIV virus envelope, gp120.
The potential vaccine was designed by Dr Anthony DeVico at the IHV, based on the idea that when gp120 binds to a CD4 molecule on the surface of a cell, it exposes hidden sites which bind to other receptors needed for the virus to enter a cell. These sites will be unable to vary much between different strains or over time, without the virus losing its ability to infect more cells. The thinking is that in the normal course of HIV infection, immune responses are drawn towards other more obvious parts of the virus which mutate to enable the virus to escape or evade the antibodies. This is why the AIDSVAX vaccines currently being tested in North America, Amsterdam and Thailand, based on gp120 alone, are only expected to protect against a limited range of HIV strains.
In principle, DeVico’s vaccine is related to the approach taken by Dr Jack Nunberg and colleagues at the University of Montana, who induced broadly neutralizing antibodies against HIV in mice by injecting them with a chemically fixed preparation of cells in which gp120 and human cell receptors were brought together. The Nunberg approach, however, does not lend itself directly to development as a vaccine, and has not been replicated since it was reported in 1999.
The next stage in developing this vaccine approach will be further testing, to see if it can directly protect animals against HIV (or SHIV) infection, and to establish its safety in human clinical trials. The US National Institutes of Health have already pledged funding to enable those early clinical trials to take place, in the next two to three years. The vaccine might also be of value to people living with HIV, though it would probably need to be combined with antiretroviral drug treatment to ensure that CD4 T-cells responding to HIV were not themselves infected by the virus.
When this was first made public, International AIDS Vaccine Initiative (IAVI) scientific director Wayne Koff said it could be a major challenge to manufacture the vaccine consistently and on a large scale.
The Institute of Human Virology continues to pursue several approaches to HIV vaccine design, one of which – using harmless forms of gut bacteria to deliver DNA as an oral vaccine – is being developed in partnership with IAVI.
The IHV news release is available here.