Does Lupus Provide the Basis for the Next HIV Vaccine?

        The immune system allows our bodies to maintain their integrity by eliminating deleterious foreign agents. The immune cells that mediate this process are highly effective and specific, contributing to the powerful nature of the immune response. However, the deregulation of immune cell activity has severe consequences. For instance, lupus is a disorder that stems from the production of self-reactive antibodies (antibodies that recognize the body's proteins). In normal individuals, immune cells that produce self-reactive antibodies are eliminated. However, individuals affected with lupus fail to clear these cells, resulting in autoimmune responses throughout the body that result in widespread inflammation, pain, and tissue destruction.

         Though the damage inflicted by lupus is extensive, one facet of the disease has been highlighted as a possible treatment option for human immunodeficiency virus (HIV) infections, which kill immune cells and dampen the immune response. Through studies of a young woman affected by both lupus and HIV, researchers at Duke University identified broadly HIV-1-neutralizing antibodies (BnAbs). These antibodies were considered unique due to their ability to recognize HIV proteins, and their presence in the woman may have alleviated the detrimental effects of HIV infection. Wonder and amazement filled many people upon the reception of this news, and some have proposed that further studies of these antibodies may lead to the formulation of new HIV vaccines.

         The findings of this study shed new light on lupus and the process that immune cells utilize to produce antibodies, but many questions remain unanswered. First, it is unclear whether BnAb production is dependent on the production of self-reactive antibodies. The authors of the study observed that BnAbs can bind to human proteins and double-stranded DNA, which suggested that BnAbs were self-reactive. This result highlighted a similarity between BnAbs and antibodies found in lupus patients, leading Duke researchers to postulate that BnAbs and self-reactive antibodies are produced by the same population of immune cells. Second, a normal immune system eliminates cells that produce BnAbs, and it is unknown whether the immune system can be coaxed into producing these antibodies safely. Stimulating a person's immune system to generate these antibodies may also encourage the production of self-reactive antibodies, which will be a dangerous side effect. Thus, more work is required to understand how these antibodies are created and the conditions that favor their production. Scientists must also consider the high mutation rate of the HIV virus, so major hurdles obstruct the possibility that this study will lead to a functional HIV vaccine.

Diagram depicting CH98 (green and blue), a broadly-reactive antibody, bound to the HIV protein gp120 (gray).

Courtesy: Bonsignori et al., The Journal of Clinical Investigation 2014