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 yearâ€™s conference got a chance to warm up with several â€œsatellite sessions.â€
One of them, â€œEffective Community Engagement in HIV Vaccine Research Among Communities and Researchers,â€ was organized by Paula Frew, PhD, director of health communications and applied community research at Emoryâ€™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.
â€œIn the past, scientists often came to the community late in the process, after a protocol for a study was already approved, and said: â€œWill you support what weâ€™ve already decided?â€ said Steve Wakefield of HIV Vaccine Trials Network. â€œThis doesnâ€™t work.â€
The Joint United Nations Programme on HIV/AIDS and AVAC presented proposed guidelines for â€œgood participatory practice,â€ analogous to good clinical practices.
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.
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?
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.
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?
Immunologist Bali Pulendran studies how those two systems work together to identify and respond to all kinds of intruders including pathogens, viruses and microbes.
Itâ€™s the innate immune systemâ€™s job to recognize the first signs of infectionâ€”that is, the moment a pathogen enters the body. â€œIn a sense they act as smoke detectors if you will,â€ says Pulendran. â€œLittle alarms.â€
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 toÂ 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:
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.Â 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 inÂ Nature Medicine from August 2009 says succinctly: “We propose that autologous GIFT15 B regulatory cells may serve as a new treatment for autoimmune ailments.”Â 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
One of the most important lessons from this past yearâ€™s pandemic, Fauci said, is the need to â€œconnect the dotsâ€ between seasonal and pandemic influenza and not view them as two separate phenomena.
â€œRather 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 donâ€™t need to go from a seasonal approach to a crisis approach.
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 H5N1â€”the virus derived from avian speciesâ€”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.
Briefly, they found that increased appetite and insulin resistance can be transferred from one mouse to another via intestinal bacteria. The results were published online by Science magazine.
Previous research indicated intestinal bacteria could modify absorption of calories, but Gewirtz and his colleagues showed that they influence appetite and metabolism (in mice)
“It has been assumed that the obesity epidemic in the developed world is driven by an increasingly sedentary lifestyle and the abundance of low-cost high-calorie foods,” Gewirtz says. “However, our results suggest that excess caloric consumption is not only a result of undisciplined eating but that intestinal bacteria contribute to changes in appetite and metabolism.”
A related report in Nature illustrates how “next generation” gene sequencing is driving large advances in our understanding of all the things the bacteria in our intestines do to us.
Gewirtz’s laboratory’s discovery grew out of their study of mice with an altered immune system. The mice were engineered to lack a gene, Toll-like receptor 5 (TLR5), which helps cells sense the presence of bacteria.
Dr. Carlos del Rio possesses a keen view of how the novel H1N1 virus emerged last spring. Del Rio was in Mexico as the virus established itself south of the border. Its rapid, far-reaching spread marked the first influenza pandemic of the 21st century.
During Emoryâ€™s fifth annual predictive health symposium, “Human Health: Molecules to Mankind,” del Rio discussed his experiences in Mexico, what weâ€™ve learned, and what novel H1N1 has to do with predictive health.Â View a video of his presentation and five lessons learned.Â
Only a day after the virus was identified, on April 23, Mexican authorities closed schools, called off sporting events, and canceled religious gatherings. Known as â€œsocial distancing,â€ these actions led to a decrease in cases, an important lesson, says del Rio. The public knew what to do, they were cooperative, and whatâ€™s more, they applied a lot of peer pressure when it came to hand washing and sneezing hygiene.
Another lesson learned: preparation paid off. Anticipating a pandemic, The World Health OrganizationÂ had earlier mandated that countries draw up influenza pandemic plans. â€œThose plans were incredibly helpful in getting people to work together, communicate, and know what to do,â€ says del Rio.Â Interestingly, the plans in Mexico and the United States were aimed at a virus projected to originate from an avian source from southeastern Asia. â€œIt was not developed for a swine virus coming from inside the country,â€ explained del Rio.
Novel H1N1, even though itâ€™s thought of as a swine virus is in fact only about 47% swine–30% from North American swine and 17% from Eurasian swine. The virus also contains human and avian strains. Thatâ€™s important, says del Rio, because the characteristics of its genes determine how symptoms, susceptibility, and immunity manifest themselves.
â€œWhat weâ€™re seeing nowadays is the new strain has crowded out the seasonal influenza virus,â€ he says. Thus far, most of the deaths from novel H1N1 have been in children, young adults, and pregnant women. â€œThe people who are dying are a very different group than in previous flu seasons,â€ says del Rio.Â
Carlos del Rio, MD
Del Rio says a lot was learned early on about the novel virus thanks to frequent and transparent international communication. This flu pandemic is really the first to occur in this era of 24-hour newscasts and the Internet. So thereâ€™s a challenge for health workers: how do you continue to communicateÂ in an effective way. â€œOne thing you say one day may be contradicted the next day because you have new information. How do you make people understand that you werenâ€™t lying to them before, but you have updated information and that information is continuously changing.”
In trying to predict whatâ€™s in store for the current flu pandemic, researchers are looking back at past pandemics. Last century, there were three major flu pandemics. The largest and most important was the 1918 pandemic.
â€œA couple of things that happened back then are very important: one was there was a second wave that was actually much more severe and much more lethal than the first one.â€ says del Rio. â€œAnd over the summer, the virus actually changed. It started very much like it did this time. It started in the spring and then we had a little blip, and then we had a big blip in the second wave, and then almost a third wave. So, clearly influenza happens in waves, and weâ€™re seeing the same thing happening this time around.â€