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In struggle against HIV, scientists get help from cows

| Wednesday, July 26, 2017, 6:00 p.m.
This June 18, 2009 file photo shows cows grazing in Rock County, Neb.
This June 18, 2009 file photo shows cows grazing in Rock County, Neb.

SAN DIEGO - Prospects for defeating HIV, once considered an invincible killer, look brighter with major advances against the AIDS-causing virus discussed at an international conference this week.

One of those pieces of good news comes from The Scripps Research Institute in La Jolla. In collaboration with the International AIDS Vaccine Initiative, its researchers have generated “broadly neutralizing antibodies” that kill HIV using an unexpected source - cows.

The startling feat was announced in a study published in the journal Nature. It marks another milestone step toward the long-elusive aim of creating a vaccine against the virus, with the antibodies perhaps also leading to creation of new HIV drugs.

“It takes humans years” for the immune system to trigger formation and full production of broadly neutralizing antibodies. “The cows solved it in a couple of months,” said Dennis Burton, co-author of the new report and a longtime researcher of such antibodies at Scripps Research.

In other news at the 9th IAS Conference on HIV Science in Paris, researchers highlighted the case of an HIV-infected child who has apparently been cured of the virus. They also announced success in using a long-lasting injection to suppress HIV levels.

Yet another study showed that certain HIV drugs were able to prevent transmission of the virus in hundreds of couples where at least one person was HIV-positive.

Despite the progress, HIV continues to spread and destroy lives, said Mark Feinberg, the vaccine initiative's president and CEO.

“To me, the most significant thing is how the epidemic continues to ravage many countries and communities, and is still such a major threat to so many people's lives,” Feinberg said. “While this disease may have receded from the headlines, it hasn't gone away. And unless things are really stepped up, it's going to get worse rather than better. That is part of the discussion taking place in Paris.”

In the United States, 1.2 million people are living with HIV. The worldwide number is 37 million, with many of the patients living in poor countries with inadequate health care. Mostly in Sub-Saharan Africa, people can't get ready access to the drugs that have turned HIV from a virtual death sentence when it was discovered in the 1980s into today's manageable disease.

And a lack of awareness of how the virus is transmitted means more are infected all the time. About 2.1 million new infections occurred worldwide in 2015, according to the National Institute for Allergy and Infectious Diseases.

Over the course of the HIV-AIDS epidemic, more than 70 million people have been infected with HIV, according to the World Health Organization. About 35 million of them have died of acquired immunodeficiency syndrome

During this time, numerous efforts have been launched to develop a vaccine against HIV. But none of those projects has demonstrated more than a modest benefit in reducing the rate of infection.

Broadly neutralizing antibodies have long been researched intensively for clues on making a better HIV vaccine. It's hard for the human immune system to produce these antibodies because HIV mutates prolifically, presenting a moving target. When these antibodies finally arrive, the virus is too well-established to eradicate from the patient's body, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

But if the immune system could be trained with a vaccine to make these powerful antibodies before any infection occurs, the virus might be blocked from getting a foothold, Fauci said.

In the study from Scripps Research and the vaccine initiative, calves were injected with HIV fragments selected to provoke production of broadly neutralizing antibodies. Their quick response was remarkable, said Burton and study co-author Vaughn Smider, a Scripps Research colleague. It's thought that the bovine immune system's powers protect it from extensive exposure to microbes in its gut as it chews and rechews its cud.

This power may be conferred by a peculiarity of cows' antibody structure.

Antibodies form a Y shape. At the ends of the two arms are loops of protein that latch onto the molecular target, called an antigen. These loops are called complementarity-determining regions, or CDRs. Their structure determines which antigens it can bind to.

An antibody region called CDR H3 is far longer in cows than in humans, which provides a greater reach to find the right molecular latching point, such as in a deep indentation that hides a vulnerable region. A broadly neutralizing human HIV antibody has an exceptionally long CDR H3 region, but is still much shorter than the one in cows.

Insights from how cows make these antibodies could help in several ways.

First, they could give guidance in devising an effective HIV vaccine that can quickly rev up the immune system to make these powerful antibodies, blocking HIV from getting a foot in the door, said Fauci, Burton and Smider.

In addition, the broadly neutralizing antibodies could be manufactured as HIV drugs to prevent or treat infection, they said. The antibodies would need to be altered to look more human so they don't provoke an immune reaction, but this has been done with other antibody drugs.

Finally, the study could provide a template for developing vaccines and therapies for other diseases, such as influenza.

While HIV and the flu virus are quite different, the general concept is the same. The most prominent targets on each mutate rapidly. Other parts, vital to the virus function, remain relatively constant but are concealed. The immune system must produce antibodies to the unchanging areas and not be distracted by areas of rapid change.

“A lot of the tools developed for HIV are now being applied to flu,” said Feinberg with the vaccine initiative. A vaccine for respiratory syncytial virus, or RSV, may be even closer at hand, he said.

“RSV has been a pathogen which causes serious morbidity and mortality in young children and older people,” Feinberg said. “And it's long been at the top of many lists for vaccine development, but for a variety of reasons has been challenging.

“I'm hopeful that these new approaches will actually crack the code on that and enable the development of an efficacious RSV vaccine. . So it is a direct example where the work in HIV is having broad benefits to other areas as well,” he added.

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