HIV Patients Hold Clues to Salmonella Vaccine Development

As we all know, HIV causes deficiencies in the immune system which lead to infections that the body would otherwise be able to fight off. In most cases these infections can be fatal and are part of what makes HIV/AIDS so destructive. Though the links between certain conditions and HIV are known, not all have been scientifically explained. One such case, until recently was Non-Typhoidal Salmonella.

Non-Typhoidal Salmonella, in high income countries, is essentially what we consider food poisoning. It causes vomiting, diarrhea, and results from eating raw foods. In low income areas it is much more destructive and for people with immune system deficiencies, in this case HIV infected people, it can be fatal. There are antibiotics for the condition but it has built an increased immunity to many of these treatments.

Though it was known that HIV prevented the body from killing the NTS cells, it was not known why. One of the researchers said of the old assumptions, "We normally think of HIV patients as being more susceptible to bacterial infections because of deficiencies in their immune systems, and often they have problems making antibodies when given vaccinations."

Yet the discovery proved quite to the contrary.

In order to kill invaders like NTS, antibodies bind to the proteins on the membranes of the invaders and consequently kill it in two ways. First, the antibody marks, or opsonizes the microbe which signals the phagocytes to ingest the cell. Secondly, some of the components collect on the membrane to form MACs or membrane attack complexes, which as we know open up a hole in the membrane.

It was discovered that in fact, HIV patients had very high levels of these antibodies which combat salmonella, yet they were still not functioning. These HIV patients had high levels of certain types of antibodies which instead of attaching to the proper point on the NTS membrane would latch on to LPS or lipopolysaccharides. The large numbers of antibodies bind to the LPS structures which effectively blocks the "killing" antibodies from binding to the cell. Though the antibodies are present, they are prevented from killing by these 'blocking' antibodies that bind to the wrong place on the cell.

When the blocking antibodies were removed, the killing antibodies went back to successfully opsonizing and MAC assembling. "In the present study, we found that it's actually an excess of antibodies that causes the problem," explained Dr MacLennan, a researcher on the project.

These findings and further investigations of LPS may lead to a vaccine which will allow those with HIV to survive NTS, a condition that is treatable for some, and should be for all.

More on antibodies:

http://en.wikipedia.org/wiki/Antibody

Supplementary info on NTS:

http://www.cdc.gov/eid/content/13/3/501.htm

-hp