HIV's link to salmonella offers vaccine clues

Research into a deadly link between salmonella and HIV shows that the AIDS virus damages the immune system in ways doctors did not previously understand, providing new clues for vaccine development.

Salmonella often causes fatal bloodstream infections in people with HIV, particularly in Africa. But although the risk has been known for more than 25 years, it is only now that researchers have a scientific explanation.

It is not immune system deficiency that causes the problem but an excess of antibodies. The discovery should help avoid blind alleys in producing new vaccines.

"It's quite a surprise and it suggests that what we are dealing with here is more of a consequence of an immune disregulation as opposed to an immune deficiency per se," said lead researcher Cal MacLennan of the University of Birmingham.

Human immunodeficiency virus (HIV) is normally thought of as a virus that stops the immune system working because it kills so-called CD4 cells that orchestrate the body's response to foreign invaders.

In the case of salmonella, however, MacLennan and colleagues found that blood from HIV-infected adults contained high levels of antibodies to salmonella. The snag was the antibodies stuck to the wrong part of the bacteria and so failed to kill them.

The research, published in the journal Science on Thursday, indicates that the body's immune response is very different in patients infected with HIV compared to those without HIV - and it is not simply a question of less immune response.

The discovery is important both for doctors trying to work out how to treat people with HIV and for developers of vaccines intended to protect HIV-positive patients against other infectious diseases.

It may also help in the hunt for an effective vaccine against salmonella, if only by showing some present approaches are misguided.

The researchers from Birmingham and the University of Malawi found the ineffective antibodies in HIV-infected Africans bound to a structure that sticks out from the surface of the salmonella known as lipopolysaccharide (LPS).

By doing so, they diverted the immune system away from the correct surface area of the bacteria and allowed them to thrive.

That is significant for vaccine developers because LPS is currently being investigated in early clinical trials as a potential target for a salmonella vaccine. "Such a vaccine could do more harm than good," MacLennan said.

SOURCE: Science, April 22, 2010.