LA JOLLA INSTITUTE SCIENTIST IDENTIFIES HELPER CELLS THAT TRIGGER POTENT RESPONSES TO HIV
Member of National AIDS Vaccine Consortium Pinpoints Helper T Cells Important for AIDS Vaccine Development
SAN DIEGO - (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 researcher 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 immune cells key in shaping the body's response to viruses
or other pathogens. The cells are multi-faceted, come in various types, and have numerous functions, including assisting
with antibody production.
"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
collaborator 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 antibody responses."
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 virus 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 cells produce antibodies, which is Crotty's area of focus.
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About La Jolla Institute
Founded in 1988, La Jolla Institute for Allergy and Immunology is a nonprofit, independent biomedical research institute
focused on improving human health through increased understanding of the immune system. Its scientists carry out research
seeking new knowledge leading to the prevention of disease through vaccines and the treatment and cure of infectious
diseases, cancer, inflammatory, and autoimmune diseases such as rheumatoid arthritis, type 1 (juvenile) diabetes,
Crohn's disease and asthma. La Jolla Institute's research staff includes more than 150 Ph.D.s and M.D.s. To
learn more about the Institute's work, visit http://www.lji.org .
Contact::
Bonnie Ward
contact@liai.org
619 - 303 - 3160
Source: La Jolla Institute
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