The Journal of Clinical Investigation has published a new study of a unique patient with an immune system that produces the types of neutralizing antibodies that are considered essential to an effective HIV vaccine response.
The patient has a rare combination of HIV and systemic lupus erythematosus or SLE, a disease where the immune system attacks the body’s own cells and tissue.
Senior author Barton F. Haynes, professor of medicine and immunology at Duke Human Vaccine Institute in the Duke University Medical Center in Durham, NC, says:
“Over the years we have searched for and now have found one person with SLE who was also chronically infected with HIV to determine if this person could make broad neutralizing antibodies.”
“We found that the patient did indeed make these important antibodies, and by determining how this immune response occurred, we have enhanced our understanding of the process involved.”
A broadly neutralizing antibody is one that is effective against many strains of a pathogen, and it protects cells from infection by blocking or neutralizing its biological effects.
One of the things that has been holding back the creation of an effective HIV vaccine has been finding a way to get the immune system to produce a broadly neutralizing antibody response.
Some people who become infected with HIV do start producing these antibodies, but it can take at least 2 years.
Nearly a decade ago, Prof. Haynes discovered some broadly neutralizing antibodies to HIV were autoreactive – they cross-reacted with the body’s tissues.
The immune system normally protects the body against autoreactive antibodies by sensing them and then stopping their production.
Prof. Haynes had a hunch that because the immune system normally keeps autoreactive broadly neutralizing antibodies in check, they are not routinely produced, and by disguising itself as body tissue, HIV avoids their clutches.
But lupus is an autoimmune disease – one where the immune system has somehow lost its ability to control autoreactive antibodies. This means the broadly neutralizing antibodies are not kept in check.
For this study, he and his colleagues identified a person with lupus who was also infected with HIV and was making broadly neutralizing antibodies.
Moreover, they were surprised to discover the patient had a broadly neutralizing antibody that was autoreactive, and this reacted with double-stranded DNA, or dsDNA molecules that are similar to those made in lupus patients who do not have HIV.
Lead author Mattia Bonsignori, assistant professor of medicine at Duke, explains:
“The cross-reactivity of the broad neutralizing antibody with dsDNA was very surprising and provided support for the hypothesis that broad neutralizing antibodies are similar to the autoantibodies that arise in lupus patients who are not infected with HIV.”
He says they are hopeful that the insights into lupus gained in the study will help them design experimental HIV vaccines that work by overcoming the immune system’s control of broad neutralizing antibodies.
The researchers were keen to point out their findings in no way suggest people with lupus are immune to HIV, and like anyone else, they should protect themselves from infection by the virus.
The National Institute of Allergy and Infectious Diseases funded the study.
Meanwhile, Medical News Today recently reported a small trial where gene therapy blocked HIV without using drugs. Researchers successfully boosted the immune system of 12 HIV patients to resist infection by removing their white blood cells, editing a gene in them, then infusing them back into the patients.