Scientist identifies helper cells that trigger potent responses to HIV

September 12, 2013

A major new finding that will significantly advance efforts to create the world's first antibody-based AIDS vaccine was published today by researchers from the La Jolla Institute for Allergy and Immunology.

La Jolla Institute scientist Shane Crotty, Ph.D., a respected vaccine and member of one of the nation's top AIDS vaccine consortiums, showed that certain helper T cells are important for triggering a strong antibody response against HIV, the virus that causes AIDS. Helper T cells are disease-fighting key in shaping the body's response to or other pathogens. The cells are multi-faceted, come in various types, and have numerous functions, including assisting with .

"We've shown that a specific type of these cells, known as follicular helper T (Tfh) cells are not only necessary, but are a limiting factor that differentiates between an average and a potent antibody response to HIV," says Crotty, a scientific with the Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID), a major research consortium led by The Scripps Research Institute.

Notably, Crotty showed that the frequency of the Tfh cells correlated with development of broadly neutralizing antibodies against HIV in a large group of HIV-infected individuals. The International AIDS Vaccine Initiative put together the group of study participants, and collaborated on the analysis.

Dennis Burton, Ph.D., a prominent HIV expert who heads the CHAVI-ID consortium at Scripps, calls the finding "the kind of fundamental basic research that will eventually allow us to defeat HIV."

"Shane Crotty and his collaborators have made an important step in understanding how potent antibodies to HIV can be made, a step which is vital to the effort to develop an AIDS vaccine given that antibodies are critical to most successful vaccines," says Burton. "Crotty is a world expert on the cells that control antibody production and, by teaming up with AIDS researchers, he and his group have shown how these cells can be tracked in blood and provided evidence of their importance in generating the right types of antibody to HIV."

The findings were published online today in the journal Immunity in a paper entitled, "Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV ."

Antibodies may be thought of as the body's smart bombs, which seek out infectious agents and tag them for destruction. Twenty-six human vaccines currently exist worldwide, 24 of which work by triggering the production of antibodies. Tfh cells are a type of CD4+ T helper cells specialized in providing help to B cells, which are the cells that make antibodies. "Essentially it's the Tfh cells that tell the B cells to produce antibodies," explains Crotty.

No vaccine currently exists for HIV (human immunodeficiency virus) and there is no cure for AIDS (acquired immune deficiency syndrome), which currently infects 34 million around the globe. While AIDS drugs have extended the lives of many sufferers, AIDS remains a major killer, particularly in developing countries, making the search for an effective HIV vaccine a public health priority.

In his study, Crotty used blood samples from HIV-infected patients and a control group of people without the disease. As part of his findings, Crotty also developed a robust test for identifying phenotypic markers for Tfh cells in the blood, a major new tool for AIDS researchers. "We found that rare HIV-infected individuals that made outstanding antibodies against HIV had higher levels of a particular kind of Tfh cells circulating in their blood than most people," he says. Further, the study showed a direct correlation between levels of Tfh cells and antibody response. "The higher the levels of Tfh cells, the more significant the antibody response," says Crotty.

Crotty says the ability to measure Tfh cells in the blood will assist AIDS vaccine researchers by serving as an indicator of antibody response. "The question has been, 'how do we make a vaccine that will stimulate those broadly neutralizing antibodies?' The need to elicit Tfh cells is one key piece of that puzzle."

The discovery is Crotty's latest major finding regarding the Tfh cells. In 2009, he drew national attention with his discovery, published in Science, illuminating a pivotal piece of the body's mechanism for switching on the production of antibodies. He proved that the BCL6 gene was like an on and off switch, or master regulator, that triggered the production of Tfh cells, which in turn told the B cells to make more antibodies. This seminal finding led to his recognition as an important scientist in vaccine design, and to his inclusion as a T cell expert in the CHAVI-ID vaccine consortium.

The consortium was one of two nationwide funded by the National Institutes of Health in 2012 in the face of new evidence from The Scripps Research Institute and others that an antibody-based HIV vaccine could be successful.

"For a long time, it wasn't thought possible," explains Crotty. "This was due to a belief that humans just don't make good antibodies against HIV and also because the is extremely changeable." But over the years rare individuals began to turn up who appeared capable of making strong antibody responses against HIV. Researchers at Scripps and other institutions began testing blood samples from these individuals in animals and found that they were producing broadly neutralizing antibodies capable of eliminating most of the HIV varieties, says Crotty. Current estimates are that only about five percent of AIDS patients can produce these potent antibodies to HIV, and only multiple years after infection.

In the CHAVI-ID consortium at Scripps, vaccine experts from across the country are collaborating to create an HIV vaccine that will trigger these strong, protective antibodies before infection. The consortium is using an integrated two-pronged approach, with one research group focusing on antibodies and B cells, and the other group exploring the role of T cells in helping B produce , which is Crotty's area of focus.

Explore further: HIV/AIDS vaccines: Defining what works

Related Stories

HIV/AIDS vaccines: Defining what works

July 18, 2013
Designing an effective HIV/AIDS vaccine is something of a paradox: a good vaccine would be safe and look enough like HIV to kick-start the immune system into neutralizing the virus – but the problem is that this is exactly ...

Researchers find potential map to more effective HIV vaccine

April 3, 2013
By tracking the very earliest days of one person's robust immune response to HIV, researchers have charted a new route for developing a long-sought vaccine that could boost the body's ability to neutralize the virus.

New microsphere-based methods for detecting HIV antibodies

May 23, 2013
Detection of HIV antibodies is used to diagnose HIV infection and monitor trials of experimental HIV/AIDS vaccines. New, more sensitive detection systems being developed use microspheres to capture HIV antibodies and can ...

New insights into HIV vaccine will improve drug development

January 10, 2013
Four years ago, a potential HIV vaccine showed promise against the virus that causes AIDS, but it fell short of providing the broad protection necessary to stem the spread of disease.

Recommended for you

New injectable antiretroviral treatment proved to be as effective as standard oral therapy

August 3, 2017
Intramuscularly administered antiretroviral therapy (ART) may be as effective for HIV treatment as current oral therapies. This is the main conclusion of a Phase II clinical trial carried out by 50 research centers around ...

Research finds home-based kit would increase HIV testing

July 31, 2017
Research led by William Robinson, PhD, Associate Research Professor of Behavioral & Community Health Sciences at LSU Health New Orleans School of Public Health, has found that 86% of heterosexuals who are at high risk for ...

Scientists divulge latest in HIV prevention

July 25, 2017
A far cry from the 1990s "ABC" campaign promoting abstinence and monogamy as HIV protection, scientists reported on new approaches Tuesday allowing people to have all the safe sex they want.

Girl's HIV infection seems under control without AIDS drugs

July 24, 2017
A South African girl born with the AIDS virus has kept her infection suppressed for more than eight years after stopping anti-HIV medicines—more evidence that early treatment can occasionally cause a long remission that, ...

Meds by monthly injection might revolutionize HIV care (Update)

July 24, 2017
Getting a shot of medication to control HIV every month or two instead of having to take pills every day could transform the way the virus is kept at bay.

Candidate AIDS vaccine passes early test

July 24, 2017
The three-decade-old quest for an AIDS vaccine received a shot of hope Monday when developers announced that a prototype triggered the immune system in an early phase of human trials.


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.