DHVI finds lupus antibodies may hold key to HIV cure
Researchers at the Duke Human Vaccine Institute recently found that a patient diagnosed with both lupus and HIV produced antibodies that limited the effects of the latter.
The broadly neutralizing antibodies produced by this patient have only been seen in the later stages of a small portion of chronically HIV-infected individuals, when it is already too late to prevent the effects of the virus, said Mattia Bonsignori, a faculty member of DHVI and the lead author of the study that discovered this. This finding, however, provides evidence that inducing these antibodies could limit HIV infection in earlier stages.
“The hypothesis was that auto-reactive broadly neutralizing antibodies weren’t being made in the vast majority of people that contract HIV because the immune system targets them as harmful,” Bonsignori said. "And we’ve got this person with lupus and HIV and bam, out of one person we’ve found broadly neutralizing antibodies.”
Lupus refers to a collection of autoimmune diseases that cause the immune system to go into hyperdrive and attack healthy tissues in the body. In contrast, HIV ultimately inhibits the immune system. The group’s finding that individuals with autoimmune diseases can limit the reproduction of the HIV virus suggests that overriding this control might be the key to engineering a vaccine, said Garnett Kelsoe, a professor of immunology and co-author of the study.
Further research is being conducted on how to safely and feasibly overcome the immune controls that prevent the production of broadly neutralizing antibodies in the general population. Laurent Verkoczy, an assistant professor in medicine and pathology and co-author of the paper, has been able to induce broadly neutralizing antibodies in mice models without autoimmune problems.
“So far, it is encouraging that no clinically adverse effects have been reported in passive transfer studies using 2F5, the broadly neutralizing antibody we have been learning how to induce in mouse models,” Verkoczy said.
The patients dually-diagnosed with HIV and lupus were "extremely important" as they provide evidence that a treatment would work in humans, he added.
“They not only show what might occur under ideal circumstances but something that actually clearly works in human populations,” Kelsoe said.
Although these findings further illustrate the path toward a future vaccine, Bonsignori stressed that this does not mean lupus itself prevents or cures HIV—rather, the effects of lupus simply set the stage for antibodies to develop that strengthen the immune system against HIV.
“The relevance of these kinds of antibodies is for vaccine development, in which you plan to elicit that kind of response before you get in touch with the virus itself,” Bonsignori said. “People with lupus, like all individuals, should protect themselves from contracting the virus in the first place.”
The preventive nature of the DHVI research distinguishes the discovery from previously documented “cures” for HIV, such as the case of Timothy Ray Brown, who received a blood stem cell transplant from a naturally HIV-resistant donor for his leukemia that eradicated his HIV infection in 2008.
“This concentrates in particular on helping us understand how we can make the immune system generate an effective broadly neutralizing antibody response, as part of a preventative vaccine—those are genetic or therapeutic cures,” Verkoczy said.