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Immunology

What if HIV was just another virus

Imagine that HIV was a “normal” virus. An infection begins and the body responds, without getting trapped in a cycle where CD4+ T cells are consumed and the immune system is crippled.

SIV can infect sooty mangabeys but it doesn't cripple their immune systems.

The attractiveness of this idea explains some of why scientists are interested in sooty mangabeys and other non-human primates. HIV’s relative SIV can infect them, but they usually don’t develop immunodeficiency.

At last week’s AIDS Vaccine 2010 conference, Cynthia Derdeyn reported her laboratory’s recent results investigating sooty mangabeys, which don’t develop high levels of neutralizing antibodies against SIV when infected. Derdeyn’s group at Emory Vaccine Center and Yerkes National Primate Research Center studies how HIV and SIV evade the immune system.

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Posted on by Quinn Eastman in Immunology Leave a comment

Re-energizing AIDS vaccine research

Emory President James Wagner welcomed participants Wednesday to the AIDS Vaccine 2010 conference in Atlanta, hosted by the Global HIV Vaccine Enterprise and locally hosted by the Emory Center for AIDS Research.

“Only occasionally are there scientific challenges that unite people powerfully towards a common goal,” Wagner said. “We are proud for the role we’ve been able to play in the pursuit of vaccine research. I am particularly pleased that so many students and young investigators have been able to participate in this conference.”

John Mascola from the Vaccine Research Center at the NIH gave the day’s first scientific talk, describing the discovery of broadly cross-reactive neutralizing antibodies to HIV and the ability to isolate those antibodies. This is the kind of recent discoveries that has re-energized the HIV vaccine research community.

Bette Korber of the Los Alamos National Laboratory noted that HIV mutations that escape immune response in some infected people are frequently susceptible in others. New “mosaic vaccines” can expand the breadth and depth of these immune responses, she said. She also described the effort underway in her laboratory to re-examine results of an earlier vaccine trial, VAX004, in light of new analytic strategies.

Giuseppe Pantaleo of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland expressed the need to implement adaptive clinical trial study design. This theme — the need to examine clinical trial results early and often, and then adapt, rather than waiting for all results at the very end of a years-long trial — has been echoed often at the conference.

At a midday press briefing, Peter Kwong of the NIH Vaccine Research Center discussed his research with broadly neutralizing antibodies, one of which attacks the initial site of vital attachment to CD4 T cells.

Hendrik Streek from Harvard’s Ragon Institute described how vaccines induce antibody and CD4 response and contraction. Even though CD4 cells are the ones attacked during HIV infection, Streek believes CD4 responses may be a missing link to effective vaccine development

Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, led a discussion of the new Enterprise Scientific Strategic Plan. Less than two out of five people who need treatment for HIV are receiving it, said Bernstein, which underscores the importance of an effective vaccine.

The new plan arrives at a time of great momentum and excitement in the field. A year of important advances has included discoveries about broadly neutralizing antibodies, new technologies, and a vaccine that demonstrated an immune response. The plan emphasizes novel clinical trials design, a strong commitment and engagement by many partners, and expanded diversity of funding by many stakeholders.

Jose Esparza, senior advisor on HIV vaccines to the Bill & Melinda Gates Foundation, emphasized the need to rapidly capitalize on new science, and said HIV vaccines are one of the foundation’s top priorities. High risk, high reward projects will be funded through the Gates Grand Challenges Explorations grants.

Posted on by Holly Korschun in Immunology Leave a comment

Strengthening community engagement in HIV vaccine research

Paula Frew, PhD

The scientific part of the AIDS Vaccine 2010 meeting began Tuesday evening with an exciting summary of issues facing the field from NIAID director Tony Fauci. But before that, participants in this year’s conference got a chance to warm up with several “satellite sessions.”

One of them, “Effective Community Engagement in HIV Vaccine Research Among Communities and Researchers,” was organized by Paula Frew, PhD, director of health communications and applied community research at Emory’s Hope Clinic.

Two prominent themes emerged from this session. The first was that community members should be involved in clinical trials at every step of the process: from design and recruitment to dissemination of results.

“In the past, scientists often came to the community late in the process, after a protocol for a study was already approved, and said: “Will you support what we’ve already decided?” said Steve Wakefield of HIV Vaccine Trials Network. “This doesn’t work.”

The Joint United Nations Programme on HIV/AIDS and AVAC presented proposed guidelines for “good participatory practice,” analogous to good clinical practices.

Another theme that emerged from the satellite session was the search for more flexible “adaptive” clinical trial formats. Glenda Gray from South Africa’s University of the Witwatersrand emphasized that adaptive trials could be faster and avoid enrollment of large numbers of patients unnecessarily.

Posted on by Quinn Eastman in Immunology Leave a comment

AIDS Vaccine 2010 conference brings global research focus to Atlanta

This week’s AIDS Vaccine 2010 conference, Sept. 28-Oct. 1, is underway at Atlanta’s Omni Hotel. Under the auspices of the Global HIV Vaccine Enterprise, the international meeting is hosted by the Emory Center for AIDS Research (CFAR).

Over 1,100 scientists, advocates, funders, and policy makers are attending 500 sessions about scientific discoveries and future directions for developing an effective HIV/AIDS vaccine. This goal is considered critical in fighting the ongoing epidemic, which newly infects 50,000 people each week around the world.

Emory HIV/AIDS researchers are playing a significant role in the meeting. The four co-chairs are Eric Hunter, PhD, co-director of the Emory CFAR; James Curran, MD, MPH, dean of Emory’s Rollins School of Public Health and co-director of the CFAR; Carlos del Rio, MD, chair of the Hubert Department of Global Health and co-chair of the CFAR; and Harriet Robinson, PhD, formerly of Yerkes Primate Center and Emory Vaccine Center and now at GeoVax, Inc.

Hunter led the opening press conference and opening session on Tuesday afternoon.

A fellowship program hosted 21 journalists from media outlets around the world.

Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, emphasized the need to build a bridge between basic science and clinical research. On Wednesday, Bernstein will talk about the Enterprise’s new strategic plan for an HIV vaccine.

Dazon Dixon Diallo, director of the African-American women’s organization Sisterlove, noted that the South has been particularly hard hit by the AIDS epidemic, with over half the HIV cases in the United States. The human rights dimensions of the disease are enormous, she said, and engagement with community partners is essential in fighting HIV. Researchers need to solve the problem with the help of people who know the most about it.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases of the NIH, said that even though the road to an HIV vaccine has been a rocky one over the past 23 years, the limited success reported last year with the RV144 trial was the first signal that it is possible for a vaccine to block HIV acquisition, a finding that has re-energized the vaccine community.

Future directions for HIV vaccine research, said Fauci, will include research that builds on insights from the success of RV144, multiple clinical trials conducted as scientific tools and not just all-or-nothing aims for vaccine licensing, more research into the early events of HIV infection that could provide targets for vaccines, and new structure-based vaccines using newly discovered neutralizing antibodies.

“I don’t think there is any question we are going to get there,” said Fauci. “The light at the end of the tunnel is the science we are now implementing.”

Press conferences are streamed live and available for playback at the conference website:

For more information on Emory’s role in the conference and Emory HIV/AIDS research, including video, see the website.

Posted on by Holly Korschun in Immunology Leave a comment

Respiratory infection may lead to weaker immunological memory

How you vaccinate helps determine how you protect. This idea lies behind many researchers’ interest in mucosal vaccines. How a vaccine is administered (orally/nasally vs intramuscular, for example) could make a difference later, when the immune system faces the bad guys the vaccine is supposed to strengthen defenses against.

How does the route of immunization affect the quality of immunity later on? For example, is a nasal spray best when trying to prevent respiratory infections?

A recent paper from Emory Vaccine Center director Rafi Ahmed’s laboratory challenges this idea. The paper was published in the Journal of Immunology. Scott Mueller, now an Australian Research Council research fellow at the University of Melbourne, is first author.

Memory T cells are a key part of a response to a vaccine, because they stick around after an infection, enabling the immune system to fight an invading virus more quickly and strongly the second time around. In the paper, the Emory team compared memory T cells that form in mice after they are infected in the respiratory system by a flu virus or throughout their bodies by a virus that causes meningitis (lymphocytic choriomeningitis virus or LCMV).

The authors engineered a flu virus to carry a tiny bit of LCMV (an epitope, in immunological terms) so that they could compare apples to apples by measuring the same kind of T cells. They found that memory T cells generated after a flu infection are weaker, in that they proliferate and stimulate other immune cells less, than after a LCMV infection. This goes against the idea that after a respiratory infection, the immune system will be better able to face a challenge in the respiratory system.

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Posted on by Quinn Eastman in Immunology Leave a comment

When your immune system calls the shots

Bali Pulendran, PhD

A tiny invader, perhaps a virus or a microbe, enters the body, and our ancient immune system responds. But how does it know what kind of invader has landed? And once it knows, how does it decide what kind of immune response it should launch?

In humans, the immune system consists of two parallel systems working with one another to fend off invaders. One is the innate immune system, the other the adaptive immune system.

Immunologist Bali Pulendran studies how those two systems work together to identify and respond to all kinds of intruders including pathogens, viruses and microbes.

It’s the innate immune system’s job to recognize the first signs of infection—that is, the moment a pathogen enters the body. “In a sense they act as smoke detectors if you will,” says Pulendran. “Little alarms.”

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2009 H1N1 flu strain could give clues to universal flu vaccine?

Last year, when the H1N1 flu epidemic was a major public health concern, a relatively low proportion of individuals getting sick were elderly, compared to previous flu epidemics. To explain this, scientists hypothesized that flu strains that circulated decades ago were similar enough to the novel swine-origin H1N1 strain to provide some immune protection.

A universal flu vaccine would eliminate the guesswork associated with the yearly flu shot

Now, researchers at Emory’s Influenza Pathogenesis & Immunology Research Center have directly tested that hypothesis in mice, and it holds up. Exposure of mice to flu strains that circulated in 1947 or 1934 induced “robust cross-protective immune responses” and can protect them against a lethal challenge with 2009 H1N1 virus, they report in Journal of Immunology.

Ioanna Skountzou and Dimitrios Koutsananos are co-first authors of the paper.

The Emory team, led by Joshy Jacob, also reports that antibodies produced in response to the 2009 H1N1 flu strain exhibit broad cross-reactivity — they react with other H1N1 strains as well as against H3N2 flu strains. They write:

The fact that the 2009 H1N1 virus can induce such cross-reactive Abs raises the intriguing possibility that viruses such as A/California/04/2009 can be used for vaccines to induce broadly cross-reactive humoral immune responses against influenza viruses. Identifying the mechanism behind this broad reactivity may enable us to design broadly cross-reactive universal influenza vaccines.

National Institute of Allergy and Infectious Diseases director Tony Fauci, when he was at Emory for the H1N1 flu conference in April, discussed the idea of a universal flu vaccine:

Posted on by Quinn Eastman in Immunology Leave a comment

Regulatory B cells: old dogs reveal their new tricks

B cells are workhorses of the immune system. Their main function is to produce antibodies against bacteria or viruses when they encounter something that they recognize. But recently researchers have been getting hints that certain kinds of B cells can also have a calming effect on the immune system. This property could come in handy with hard-to-treat conditions such as graft-vs-host disease, multiple sclerosis, or Crohn’s disease.

Hematologist Jacques Galipeau has found that B cells treated with an artificial hybrid molecule called GIFT15 turn into “peacemakers”. These specially treated B cells can tamp down the immune system in an experimental animal model of multiple sclerosis, suggesting that they could accomplish a similar task with the human disease.

Galipeau’s paper in Nature Medicine from August 2009 says succinctly: “We propose that autologous GIFT15 B regulatory cells may serve as a new treatment for autoimmune ailments.” Galipeau, a recent arrival to Emory from McGill University in Montreal, explains this tactic and other aspects of personalized cell therapy in the video above. Read more

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NIAID Director Fauci: link seasonal and pandemic flu preparedness

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, delivered the keynote address Sunday, April 18, as part of a three-day conference on H1N1 Virus: The First Pandemic of the 21st Century, sponsored by the Emory-UGA Influenza Pathogenesis and Immunology Research Center.

One of the most important lessons from this past year’s pandemic, Fauci said, is the need to “connect the dots” between seasonal and pandemic influenza and not view them as two separate phenomena.

Fauci enthusiastically supports the CDC’s call for universal flu vaccination.

“Rather than trying to figure out one priority group over another,” Fauci said, “if we can get into a rhythm of getting most people vaccinated each year, we will have most of the population with some degree of immunity. We will get into a situation where we don’t need to go from a seasonal approach to a crisis approach.

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Posted on by Holly Korschun in Immunology Leave a comment

Moving flu vaccine research forward

The scientists in the lab of Richard Compans, PhD, professor of microbiology and immunology at Emory, are hard at work, imagining the unimaginable: A time when patients can self-administer flu vaccines. A time when vaccination does not require exposure to inactive viruses. A time when a universal vaccine could protect from all varieties of influenza: swine, avian, seasonal and strains still emerging.

Richard Compans, PhD (right), with colleague Mark Prausnitz, PhD, from Georgia Tech

But it’s not just hope that motivates them as they work. Emory’s scientists are fighting the clock against another possible future: a time of pandemic and uncontrollable virus mutation. The recent emergence of H1N1 and H5N1, known colloquially as swine flu and avian flu, have added an even greater sense of urgency to their task.

“The H5N1—the virus derived from avian species—has a 60 percent mortality,” says Emory microbiologist Sang-Moo Kang, PhD. Yet that strain of influenza hasn’t resulted in many human deaths, because, so far, avian flu spreads only to humans who are in contact with infected birds.

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Posted on by Jennifer Johnson in Immunology Leave a comment