Barrier to autoimmune disease may open door to HIV, study suggests

July 11, 2017, Rockefeller University Press
HIV infecting a human cell. Credit: NIH

Researchers from the University of Colorado School of Medicine have discovered that a process that protects the body from autoimmune disease also prevents the immune system from generating antibodies that can neutralize the HIV-1 virus. The findings, which will be published July 11 in The Journal of Experimental Medicine, might be considered by scientists trying to develop a vaccine that can stimulate the production of these neutralizing antibodies.

Some patients infected with HIV-1, the virus that causes AIDS, develop "broadly neutralizing antibodies" (bnAbs) that can protect against a wide variety of HIV-1 strains by recognizing a protein on the surface of the virus called Env. But the patients only develop these antibodies after many years of infection. Researchers are keen to discover how such bnAbs can be induced quickly in response to vaccinations against HIV-1.

bnAbs have several unusual features, including the fact that some of them often also recognize some of the body's own proteins. HIV-1-infected individuals may therefore take a long time to develop these antibodies because their production is suppressed by some of the mechanisms that prevent the body from generating self-reactive antibodies that could target healthy tissues and cause autoimmune diseases such as systemic lupus erythematosus (SLE). Patients with SLE show lower rates of HIV-1 infection, possibly because they produce self-reactive antibodies that can also recognize and neutralize HIV-1. Indeed, researchers recently identified one SLE patient who, though infected with HIV-1, could control her infection without the aid of antiretroviral drugs because she produced large amounts of bnAbs.

The process by which healthy individuals prevent the production of self-reactive antibodies is called immunological tolerance. B cells carrying potentially self-reactive antibodies can be eliminated while they are still developing in the bone marrow. And any self-recognizing B cells that escape this fate and enter the circulation are generally suppressed by the immune system so that they cannot mature into plasma cells that can secrete large amounts of the self-reactive antibody.

In the current study, a team of researchers led by Raul M. Torres, Professor of Immunology and Microbiology at the University of Colorado School of Medicine, investigated whether breaking these immunological tolerance mechanisms to allow the production of self-reactive antibodies would also facilitate the production of antibodies capable of neutralizing HIV-1.

The researchers first tested mice with genetic defects that cause lupus-like symptoms and found that many of these mice produced antibodies that could neutralize HIV-1 after they were injected with alum, a chemical that promotes antibody secretion and is often used as an adjuvant in vaccinations.

Next, the researchers treated normal, healthy mice with a drug that impairs immunological tolerance and found that these animals started to produce antibodies somewhat capable of neutralizing HIV-1. The production of these antibodies was increased by alum injection and, if the mice were also injected with the HIV-1 protein Env, the mice produced potent bnAbs that were able to neutralize a range of HIV-1 strains.

In all cases, the production of HIV-1 neutralizing antibodies correlated with the levels of a self-reactive antibody that recognizes a chromosomal protein called Histone H2A. The researchers purified these anti-H2A antibodies and confirmed that they were able to neutralize HIV-1.

"We think this may reflect an example of molecular mimicry where HIV-1 Env has evolved to mimic an epitope on histone H2A as a mechanism of immune camouflage," says Torres.

Immunological tolerance eliminates or suppresses any B cells capable of producing antibodies that recognize histone H2A, thereby limiting the ability to produce bnAbs.

"But breaching peripheral immunological tolerance permits the production of cross-reactive able to neutralize HIV-1," says Torres. "As this study was performed in an animal model, it will of course be important to determine its relevance for HIV immunity in humans. Here, primary consideration will be determining whether immunological tolerance can be transiently relaxed without leading to detrimental autoimmune manifestations and as a means to possibly elicit HIV-1 bnAbs with vaccination."

Explore further: Mechanism found for development of protective HIV antibodies

More information: Schroeder et al., Journal of Experimental Medicine (2017). DOI: 10.1084/jem.20161190

Related Stories

Mechanism found for development of protective HIV antibodies

July 24, 2014
Scientists at Duke Medicine have found an immunologic mechanism that makes broadly neutralizing antibodies in people who are HIV-1 infected.

Antibody combination puts HIV on the ropes

January 25, 2017
Without antiretroviral drug treatment, the majority of people infected with HIV ultimately develop AIDS, as the virus changes and evolves beyond the body's ability to control it. But a small group of infected individuals—called ...

Broadly neutralizing HIV antibodies engineered to be better vaccine leads

August 25, 2016
One approach to HIV vaccine development relies on broadly neutralizing antibodies (bnAbs) that protect against different circulating HIV strains. bnAbs have been isolated from HIV-infected individuals, but they are highly ...

Scientists discover HIV antibody that binds to novel target on virus

September 3, 2014
An NIH-led team of scientists has discovered a new vulnerability in the armor of HIV that a vaccine, other preventive regimen or treatment could exploit. The site straddles two proteins, gp41 and gp120, that jut out of the ...

Scientists identify immunological profiles of people who make powerful HIV antibodies

July 29, 2016
One of the main mysteries confounding development of an HIV vaccine is why some people infected with the virus make the desired antibodies after several years, but a vaccine can't seem to induce the same response.

Recommended for you

HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection

January 18, 2018
A first-of-its-kind study has found that the genetic diversity of human immunodeficiency virus type 1 (HIV-1) is higher in the vaginal tract than in the blood stream during early infection. This finding, published in PLOS ...

War in Ukraine has escalated HIV spread in the country: study

January 15, 2018
Conflict in Ukraine has increased the risk of HIV outbreaks throughout the country as displaced HIV-infected people move from war-affected regions to areas with higher risk of transmission, according to analysis by scientists.

Researchers offer new model for uncovering true HIV mortality rates in Zambia

January 12, 2018
A new study that seeks to better ascertain HIV mortality rates in Zambia could provide a model for improved national and regional surveillance approaches, and ultimately, more effective HIV treatment strategies.

New drug capsule may allow weekly HIV treatment

January 9, 2018
Researchers at MIT and Brigham and Women's Hospital have developed a capsule that can deliver a week's worth of HIV drugs in a single dose. This advance could make it much easier for patients to adhere to the strict schedule ...

New long-acting, less-toxic HIV drug suppresses virus in humanized mice

January 8, 2018
A team of Yale researchers tested a new chemical compound that suppresses HIV, protects immune cells, and remains effective for weeks with a single dose. In animal experiments, the compound proved to be a promising new candidate ...

Usage remains low for pill that can prevent HIV infection

January 8, 2018
From gritty neighborhoods in New York and Los Angeles to clinics in Kenya and Brazil, health workers are trying to popularize a pill that has proven highly effective in preventing HIV but which—in their view—remains woefully ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.