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Researchers from Thomas Jefferson University are one step closer to developing a vaccine against the AIDS disease.

Led by Matthias J. Schnell, Ph.D., director of the Jefferson Vaccine Center, the researchers found that a rabies virus-based vaccine administered to monkeys protected against the simian equivalent of the HIV virus (SIV). The data were published in the journal Vaccine.

The researchers previously showed that a rabies-based vaccine expressing HIV and SIV antigens protective against a chimeric HIV/SIV virus in monkeys. In this study, they used highly attenuated rabies virus vaccine vectors to protect against challenge with the highly pathogenic SIVmac251. This type of SIV virus causes a more similar disease in monkeys compared to human infection with HIV-1. In addition, it is difficult to protect monkeys against AIDS-like disease after challenge with SIVmac251.

Two vaccine strategies were used: immunization with a recombinant rabies virus expressing SIVmac239GagPol, or a combination of that and a rabies virus expressing SIVmac239Env. Both strategies induced neutralizing antibody production, CD8+ T cell responses, and increased protection. Although the combination with Env helped immediately following the infection, the long-term benefits were minimal. However, it was surprising that the rabies-based vaccine was able to induce such potent anti-SIV humoral responses.

“Although we can’t yet block the infection, we showed that we can protect against disease,” said Dr. Schnell. “We also saw significant antibody activity against the virus, which is promising. In addition, this is a very simple approach that only took two immunizations.”

Source: Emily Shafer

Thomas Jefferson University

Scientists seeking to understand how to make an AIDS vaccine have found the cause of a major roadblock. It turns out that the immune system can indeed produce cells with the potential to manufacture powerful HIV-blocking antibodies - but at the same time, the immune system works equally hard to make sure these cells are eliminated before they have a chance to mature.

“These studies show that a potentially protective neutralizing antibody against a viral disease is under the control of immunological tolerance,” said Barton Haynes, M.D., director of the Center for HIV/AIDS Vaccine Immunology (CHAVI) at Duke University Medical Center and senior author of the study appearing in the online early edition of the Proceedings of the National Academy of Sciences. “This represents a new insight into the way HIV effectively evades detection by the B cell arm of the immune system and may offer new directions for vaccine design.”

Over the years, scientists have assumed that B cells - one of the first lines of defense against infection - are simply not able to “see” the HIV virus. HIV has the ability to hide its most vulnerable parts from immune system surveillance, and researchers generally assumed that helped explain why B cells often took weeks and even months to arise following infection.

But several years ago, Duke researchers hypothesized that the antibodies required to broadly neutralize HIV may not be produced in the first place because the immune system “sees” them as a potential threat - due to their similarity to antibodies that promote autoimmune disease - and destroys them.

To see if this is indeed what happens, Laurent Verkoczy, Ph.D., assistant professor of medicine at Duke and the lead author of the study, and Haynes genetically engineered a mouse that could only produce B cells containing a rare but potent broadly neutralizing human antibody that is able to block HIV infection.

Researchers found that the mouse’s immune system produced plenty of early stage B cells bearing this human neutralizing antibody on their surface but eliminated most of them before they had a chance to fully evolve into more mature B cells capable of secreting the antibody.

“This work may mean that we need to think and act very differently in envisioning how a successful vaccine may work,” said Verkoczy. “The good news is that while about 85 percent of the “right” kind of B cells are eliminated, about 15 percent survive and wind up in circulating blood, but are turned off. One goal in vaccine design may be to figure out how to wake them up so they can go to work.”

“We have now unveiled a major reason why members of this class of neutralizing antibodies are not routinely made: Our own immune systems block their production because they are perceived as potentially harmful, when in reality, they are not,” said Haynes. “This is a very unusual way the virus has developed to evade the immune system.”

Haynes says researchers plan on using the new mouse model to test ways to teach the immune system to enable the production of powerful neutralizing antibodies capable of blocking HIV.

The research was supported by the Bill and Melinda Gates Foundation, the Duke Center for AIDS Research, and grants from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Duke colleagues who contributed to the research include T. Matt Holl, Hilary Bouton-Verville, S. Munir Alam, Hua-Xin Liao and Garnett Kelsoe. Additional co-authors include Marilyn Diaz, from the National Institute of Environmental Health Sciences and Ying-Bin Ouyang, of Xenogen Biosciences.

Source: Michelle Gailiun

Duke University Medical Center

The Hebrew University of Jerusalem Kuvin Center for the Study of Infectious and Tropical Diseases has received a $5 million grant from the Bill & Melinda Gates Foundation for research into visceral leishmaniasis in Ethiopia.

The project will be led by Prof. Alon Warburg, a vector biologist working at the Institute of Medical Research Israel-Canada at the Hebrew University’s Faculty of Medicine.

The project, entitled ‘Studies on the ecology and transmission dynamics of visceral leishmaniasis in Ethiopia’, will comprise thorough investigations to determine the drivers of transmission of Kala-Azar in endemic foci. The ecology of the sand fly vectors and their larval breeding habitats will be characterized and putative reservoir hosts will be incriminated. In parallel, genotypes and drug sensitivities of the Leishmania parasites will be studied in depth. The data gathered will be rigorously analyzed and utilized to identify the weak links in the transmission cycle in order to devise methods for control of the disease.

According to Prof. Warburg, “Visceral leishmaniasis is transmitted by small, mosquito-like insects known as sand flies. Sand flies become infected with Leishmania while sucking blood from an infected person or animal and transmit the disease during subsequent blood meals. Sand fly control is problematic because the breeding sites of their immature stages are unknown, making larval source reduction all but impossible.”

An estimated 500,000 cases of visceral leishmaniasis - also known as Kala-azar - occur annually. More than 90 percent of the cases are concentrated in the Indian sub-continent, East Africa and Brazil. The worst affected region in Africa is southern Sudan and northwest Ethiopia. Kala Azar is considered an emerging disease in Ethiopia where it is frequently associated with HIV/AIDS, a leading cause of adult illness and death. Leishmania donovani parasites multiply inside cells of the immune system producing symptoms that include an enlarged spleen and fevers. If treated with a 30-day course of intra-muscular injections, the cure rate is 95 percent. However, if left untreated, Kala-azar kills 95 percent of its victims.

Co-infection with HIV makes treatment much more complex. Because the immune system is suppressed in HIV-positive patients, Kala-azar relapses are common and patients have to be treated multiple times. Given the difficulties of treating large populations in remote areas and the bleak prospects for co-infected patients, efforts must be made to protect people living in HIV/AIDS-endemic areas from contracting Kala-azar.

This is a collaborative project with Prof. Asrat Hailu from the Faculty of Medicine and Prof. Teshome Gebre-Michael of the Aklilu Lemma Institute of Pathobiology in Addis Ababa University. Additional collaborating institutions include the Hebrew University’s Robert H. Smith Faculty of Agriculture, Food and Environment, Charles University in Prague, the Volcani Center and the Gertner Institute for Trauma and Emergency Medicine Research.

Source: Jerry Barach

The Hebrew University of Jerusalem

Michael Saag, M.D., director of the University of Alabama at Birmingham (UAB) Center for AIDS Research and a renowned leader in the establishment of best practices for human immunodeficiency virus (HIV) treatment, has been installed as chair of the board of directors of the HIV Medicine Association (HIVMA).

HIVMA is the largest professional society of physicians, scientists and health-care professionals dedicated to the field of HIV and AIDS. The organization actively promotes quality in HIV care and advocates for policies that ensure a science-based, comprehensive and humane response to the AIDS pandemic, including adequate funding for HIV research, prevention, care and provider training and resources.

A professor of medicine, Saag also directs UAB’s Division of Infectious Diseases. He is on the board of directors of the International AIDS Society-USA, and he helped author U.S. Department of Health and Human Services guidelines for antiretroviral treatments and edits the Sanford Guide to HIV/AIDS Therapy. Saag will serve a one-year term with HIVMA that ends November 2010.

Saag is credited with being the first to demonstrate the value of viral-load testing in a clinical practice. This test allows physicians to follow the response to antiretroviral treatment, just as they follow the blood-sugar response to insulin when treating diabetics. He also is among the first to perform clinical trials of several antiretroviral drugs that are approved worldwide.

Saag helped establish UAB’s 1917 Clinic, a comprehensive HIV outpatient clinic devoted to patient care and clinical-trial coordination. Opened in 1988, the clinic has grown into a hub for HIV basic science and treatment-outcomes research at UAB.

He has authored dozens of scientific manuscripts, contributed more than 50 chapters to medical textbooks and served on the editorial board of the journal AIDS Research and Human Retrovir uses. He also has served on subspecialty committees of the American Board of Internal Medicine and the American College of Physicians.

Saag earned his medical degree from the University of Louisville in Kentucky and completed a postdoctoral fellowship at UAB. He is the Jim Straley Chair in AIDS Research and an active member of the American Society of Clinical Investigation.

About the HIV Medicine Association

The HIV Medicine Association (HIVMA) is the professional home for more than 3,600 physicians, scientists and other health-care professionals dedicated to the field of HIV/AIDS. A part of the Infectious Diseases Society of America, HIVMA promotes quality in HIV care and advocates policies that ensure a comprehensive and humane response to the AIDS pandemic informed by science and social justice. For more information, visit http://www.hivma.org.

About the UAB Center for AIDS Research

The UAB Center for AIDS Research (CFAR) is one of the seven original centers established in 1988 by the federal government to stimulate research and advances in fighting AIDS and HIV. CFAR supports prevention and HIV-patient care at the 1917 Clinic and in Africa through a partnership with the Center for Infectious Disease Research in Zambia.

Source
University of Alabama at Birmingham

A scientist who is helping to treat thousands of people living with HIV and tuberculosis (TB) in South Africa was awarded the Royal Society Pfizer Award at a ceremony last night (27 October). Dr Linda-Gail Bekker’s research looks at how TB epidemiology has changed in the HIV era. Researchers estimate that more than one in ten of all South Africans over 2 years old were living with HIV in 2008. South Africa has also seen a six fold increase in tuberculosis rates in the last 20 years.

The Royal Society Pfizer Award includes a £60,000 award grant which aims to encourage medical research in Africa by supporting young scientists. Pfizer, the world’s leading research-based pharmaceutical company has been supporting the awards for the last four years and has so far granted £240,000 core funding for research work in Africa.

Dr Bekker is deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town and chief operating officer of the Desmond Tutu HIV Foundation. Her doctoral work focused on the host response to TB both with and in the absence of HIV co-infection. Subsequently her research interests have expanded to include programmatic and action research around antiretroviral roll out, TB integration and prevention of HIV.

The funding provided by this award will help with research being carried out at Nyanga Primary Health Clinic in Cape Town. Bekker’s team will collect positive tuberculosis cultures obtained from sputum samples in the clinic with the specific aim of describing the diversity of TB strains among HIV-positive individuals receiving Highly Active Anti-Retrovir al Treatment (HAART), HIV- positive individuals not receiving HAART and HIV negative individuals. They will also explore healthcare-associated transmission of tuberculosis in the clinic and test drug sensitivities of all cultures. It is hoped the research will have lessons for how TB/HIV and ART services are designed and run in southern Africa as well as giving further information on host susceptibility and organism virulence.

Dr Bekker said of her award:

“In 2005, the World Health Organization declared a regional emergency and called for extraordinary measures to be implemented to curb the unprecedented increase in HIV/TB currently occurring in South and southern Africa. I am so honoured to be a recipient of the Royal Society Pfizer Award this year- it will help me and the great team I work with to do our part in investigating urgently what those extraordinary measures should be. More than ever before this public health crisis requires innovative thought and research to find novel answers and effective strategies to turn these numbers around.”

Professor Ralph Kirsch, a colleague of Dr Bekker’s at the University of Cape Town, said:

“Linda Gail marries science and humanity in her approach to patients with HIVAIDS. She is constantly looking at how to provide better care and how to make compliance easier. Her relationship with her patients and with those recruited into her various studies is an important role model to us all.”

Professor Lorna Casselton, Foreign Secretary of the Royal Society, said:

“The Royal Society Pfizer Award recognises the valuable research already taking place in Africa, whilst aiming to expand research capacity. We hope that this award will continue to boost the careers of its winners and the individuals working around them. This year’s winner, Dr Linda-Gail Bekker, has done outstanding research into tuberculosis and HIV co-infections in Africa. Her contribution to several innovative and successful health delivery platforms and capacity building opportunities has been invaluable. We congratulate her and hope that this funding will help her continue her research to its full potential.”

Dr Freda Lewis-Hall, Chief Medical Officer of Pfizer Inc, said:

“Defeating infectious disease means making advances in both prevention and treatment. Pfizer is proud to be a partner with the Royal Society in creating this award, which recognizes essential and inspiring medical and public health research from a new generation of African scientists. Support like this translates into new knowledge, lives extended and saved, and less human pain and suffering.”

The award grant and a £5,000 personal prize were presented to Dr Bekker at a ceremony at the Royal Society in London last night.

Source
The Royal Society

Federal health officials are preparing to study the “test and treat” strategy in an effort to curb the spread of HIV in high-incidence communities, the New York Times reports. The three-year study will focus on Washington, D.C., where as many as 5% of adults are HIV-positive, and the Bronx, which has the highest rate of AIDS-related deaths of any New York City borough. Both communities have some of the highest HIV/AIDS rates in the U.S. According to Centers for Disease Control and Prevention data, 20% to 25% of people in the U.S. are unaware of their HIV-positive status. CDC recommends voluntary HIV testing as part of regular medical care for people ages 13 to 64, but experts say that many hospitals, clinics and medical practices are not following the recommendations.

According to the Times, the test and treat strategy involves routinely testing nearly every adult in a community and immediately beginning treatment for those found to be HIV-positive. The goal of the study’s first phase is not to determine if the strategy can slow an epidemic, but rather if it can be carried out effectively given the number of barriers to HIV testing and treatment, the officials said. For example, only about 50% of Washington, D.C., residents who tested HIV-positive in 2006 saw a physician about the diagnosis within six months (Okie, New York Times, 10/27).

Reprinted with kind permission from http://www.nationalpartnership.org. You can view the entire Daily Women’s Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women’s Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.

© 2009 The Advisory Board Company. All rights reserved.

Two Yale School of Medicine physicians have been awarded a $4.1 million research grant from the National Institutes of Health (NIH) to study a new pharmacological treatment for newly released HIV-positive inmates with alcohol dependence who are transitioning back into the community.

The U.S. prison population is disproportionately impacted by HIV and by alcohol and drug abuse. A majority of HIV-positive inmates also have substance abuse disorders. Though many are treated successfully for both HIV and substance abuse while incarcerated, they face enormous challenges when released.

“Released HIV-positive inmates who relapse to alcohol and drug use are less likely to adhere to HIV treatment, including antiretroviral drugs, and more likely to engage in high-risk behavior,” according to Frederick L. Altice, M.D., professor at Yale School of Medicine, director of clinical and community research at the Yale AIDS Program and one of the two principal investigators.

The prestigious NIH grant is the first of its stature for Sandra Springer, M.D., assistant professor of medicine and co-principal investigator - a junior investigator whose career has already benefited from a career development award from the NIH. In the clinical trial led by Springer and Altice, 125 HIV-positive prisoners with alcohol dependence who are transitioning back into society will receive subcutaneous (depot) injections of naltrexone. Though the medication has been previously shown to benefit those with alcohol dependence, HIV-infected individuals were never previously included in clinical trials.

All subjects in the trial, whether getting naltrexone or the placebo, will receive comprehensive case-management services and 24 weeks of counseling. “This is the first time that depot naltrexone will be formally tested in HIV-infected patients,” says Springer. She adds, “We hope to learn whether a medication known to benefit those with alcohol problems will also help assist with HIV treatment and prevent a relapse to high-risk behaviors. Our study could confirm that treating one disease, alcohol dependence, can actually fight two life-threatening conditions.”

Source
Yale University

View drug information on Naltrexone Hydrochloride Tablets.

Mobile phones are on the verge of becoming powerful tools to collect data on many issues, ranging from global health to the environment.

Computer scientists at the University of Washington have used Android, the open-source mobile operating system championed by Google, to turn a cell phone into a versatile data-collection device. Organizations that want a fully customizable way to, say, snap pictures of a deforested area, add the location coordinates and instantly submit that information to a global environmental database now have a flexible and free way to do it.

UW computer scientists were already working on mobile tools for the developing world when Android, the first comprehensive open-source platform for mobile devices, was announced two years ago by the Open Handset Alliance, a group of companies of which Google is a member. For the past year UW computer science and engineering doctoral students Carl Hartung, Yaw Anokwa and Waylon Brunette have worked at Google’s Seattle office using Android to create a data-collection platform for use in developing regions.

Their free suite of tools, named Open Data Kit, is already used by organizations around the world that need inexpensive ways to gather information in areas with little infrastructure. Seattle’s Grameen Foundation Technology Center is using it to evaluate its Ugandan text-messaging information hotline; D-Tree International, a Boston-based nonprofit, is using it in Tanzania to guide health workers treating children under 5 years old; the University of California, Berkeley’s Human Rights Center is using it to record human rights violations in the Central African Republic. This fall the Jane Goodall Foundation in Tanzania and the Brazilian Forest Service signed up to use it to monitor deforestation.

“Many organizations need to be able to make evidence-based decisions, and to do that they need data,” Anokwa said. “We hope our toolkit enables organizations to gather the data quickly so they can analyze it quickly and make the best decisions for the communities they serve.”

They tool is described in an article published this month in the Institute of Electrical and Electronics Engineers’ Computer magazine. Gaetano Borriello, UW professor of computer science and engineering, and Adam Lerer, a graduate student at the Massachusetts Institute of Technology, are co-authors.

In the past some researchers have harnessed individual cell phone models to collect data in the field. But when the phone gets outdated, so does the software. Instead of creating a tool for a single phone, or even a single purpose, the UW team built something that would provide a reusable platform to collect all types of mobile data.

“We found a lot of organizations were building a lot of one-off tools that were very similar,” Hartung said. “We’re trying to make ours as compatible and flexible as possible.”

Open Data Kit’s versatile suite of tools can collect data; store, view and export data on remote servers; and manage devices in the field from a central office. The output is compatible with emerging data standards such as the Open Medical Records System, which aims to coordinate health records in the developing world.

Many organizations are using Open Data Kit, but the biggest project so far is a major effort to track and treat HIV patients in Kenya. Led by the Academic Model Providing Access to Healthcare, a U.S. Agency for International Development-funded partnership between Indiana University and Kenya’s Moi University, it is one of the most comprehensive HIV treatment programs in sub-Saharan Africa. AMPATH trains Kenyan community health workers who conduct door-to-door testing in rural areas for HIV, tuberculosis and malaria, and offer ongoing personalized health counseling.

Hartung and Anokwa traveled to Kenya this summer to meet with AMPATH’s community health workers and do a trial run with 10 phones. They spent two weeks working with Kenyan collaborators, then accompanied community health workers on home visits to see the phone being used in the field.

“It’s a pretty amazing experience to be sitting in a mud hut seeing someone get counseled, maybe for the first time, on HIV, and the counselor is using your tool to record information,” Hartung said. “It gives a whole new perspective on the need for reliable software.”

For the past two years AMPATH workers have conducted field visits using a Palm Pilot and separate GPS unit. This required workers to key in a 10-digit identifier for each patient, stand outside and wait up to two minutes to get location coordinates, and at the end of each day return to the main office to upload their information to a central database, which adds travel time and expense.

Phones running Open Data Kit can record location in seconds, scan a barcode rather than requiring the numbers to be entered by hand, and upload the data automatically using a cellular network. AMPATH plans to deploy 100 Google-powered phones by the end of this year. Ultimately, it aims to use 300 phones powered with Open Data Kit to reach 2 million people.

“Adopting this technology was kind of a win-win-win in terms of direction for our organization,” said Dr. Burke Mamlin, an assistant professor of medicine at the Indiana University School of Medicine and research scientist with the nonprofit Regenstrief Institute, which supports AMPATH. “This opens doors by allowing us to bring data collected in the field directly into our medical records system. And now we have a phone, all the personal digital assistant capability, the ability to read barcodes, and the ability to capture images or video, all in one unit.”

The device also opens up new possibilities for the future. If one family member is absent during a site visit health workers can schedule a follow-up visit and have it automatically appear in their calendars. Health workers could cue up public-health videos if they thought the family could benefit. Program managers in a central office could track data in real time and send updates to field workers without them having to come back to the base.

Building technology for use in the developing world offers new challenges for computer scientists. Power and connectivity may be intermittent, and users may have poor eyesight or literacy.

There are also other issues specific to mobile devices. Web developers in the Western world generally create white text on a dark background, but it turns out dark text on a white background works better in bright sunlight, where most of these devices will be used. And touch-screen phones rely on an electrical signal from users’ fingers, but that signal gets blocked by calluses. UW students found some rural users needed to use a softer part of the finger pad, and this meant designing bigger buttons.

The team is now back at the UW, where they are part of a group called Change that studies technology in the developing world. Funding for the project comes from Google.org, the philanthropic arm of the company. The code is freely available and ongoing research will be based at the university. Hartung and Anokwa are co-teaching a new course this fall, Mobile and Cloud Applications for Emerging Regions (http://www.cs.washington.edu/education/courses/cse599y/09au/), in which undergraduate computer science and engineering students learn skills and then apply them by creating new features requested by Open Data Kit users.

“We’ve only seen the tip of the iceberg in terms of the types of applications we can run that are really customized to the person who’s holding the device,” said Gaetano Borriello. “For places where resources are constrained, where data is unavailable and where large problems exist, this technology is very powerful.”

More information on Open Data Kit is at http://change.washington.edu/projects/odk. Watch a demonstration of the tool on YouTube at http://tinyurl.com/lttrqj

Source: Hannah Hickey

University of Washington

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