Published on September 20, 2013 at 9:01 AM
In several ongoing studies, the TSRI team and others are working out how to make a vaccine that stimulates the production of 4E10, b12 and other broadly neutralizing anti-HIV antibodies. However, this latest study indicates that this approach might be complicated by unwanted self-reactivity. Antibodies that cross-react with host tissue—like 4E10 has now been shown to do—are associated with autoimmune diseases such as multiple sclerosis and lupus.
The TSRI study also raises the question of how 4E10 was generated in the first place. According to Nemazee, 4E10 may be a fluke, cropping up in an HIV patient who was also prone to autoimmune diseases. Alternatively, the autoreactive antibody could have arisen in the patient as a consequence of the disease—perhaps the body's normal mechanism for weeding out such antibodies failed, allowing the serendipitous production of an anti-HIV antibody.
Despite this new concern, there is still hope for 4E10's role in HIV vaccine development. A companion paper published in the same issue of The Journal of Immunology (http://www.jimmunol.org/content/191/6/3179.long) found that another potent, broadly neutralizing anti-HIV antibody, b12, was not self-reactive and could respond to a candidate vaccine preparation provided by Richard Wyatt, TSRI Professor of Immunology and Director of Viral Immunology at the International AIDS Vaccine Initiative Neutralizing Antibody Center.
"It's still possible that we could safely elicit the 4E10-like antibody in order to protect against HIV," Nemazee said. "We just have to think about how to generate the best antibodies without causing other problems. We have a lot of questions. And now we have a good model to help us answer them."