Caltech-Developed Method for Delivering HIV-Fighting Antibodies Proven Even More Promising

In 2011, biologists at the California Institute of Technology (Caltech) demonstrated a highly effective method for delivering HIV-fighting antibodies to mice—a treatment that protected the mice from infection by a laboratory strain of HIV delivered intravenously. Now the researchers, led by Nobel Laureate David Baltimore, have shown that the same procedure is just as effective against a strain of HIV found in the real world, even when transmitted across mucosal surfaces.

http://www.caltech.edu/media_colorbox/6479/colorbox/en

The findings, which appear in the February 9 advance online publication of the journal Nature Medicine, suggest that the delivery method might be effective in preventing vaginal transmission of HIV between humans.

“The method that we developed has now been validated in the most natural possible setting in a mouse,” says Baltimore, president emeritus and the Robert Andrews Millikan Professor of Biology at Caltech. “This procedure is extremely effective against a naturally transmitted strain and by an intravaginal infection route, which is a model of how HIV is transmitted in most of the infections that occur in the world.”

The new delivery method—called Vectored ImmunoProphylaxis, or VIP for short—is not exactly a vaccine. Vaccines introduce substances such as antigens into the body to try to get the immune system to mount an appropriate attack—to generate antibodies that can block an infection or T cells that can attack infected cells. In the case of VIP, a small, harmless virus is injected and delivers genes to the muscle tissue, instructing it to generate specific antibodies.

The researchers emphasize that the work was done in mice and that the leap from mice to humans is large. The team is now working with the Vaccine Research Center at the National Institutes of Health to begin clinical evaluation.

The study, “Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission,” was supported by the UCLA Center for AIDS Research, the National Institutes of Health, and the Caltech-UCLA Joint Center for Translational Medicine. Caltech biology researchers Alejandro B. Balazs, Yong Ouyang, Christin H. Hong, Joyce Chen, and Steven M. Nguyen also contributed to the study, as well as Dinesh S. Rao of the David Geffen School of Medicine at UCLA and Dong Sung An of the UCLA AIDS Institute.

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Study is first to explain type of antimalarial drug resistance

WASHINGTON — A Georgetown University professor published in the online journal PLOS ONE the first study explaining why drugs designed to fight off malaria stop working in some people with the disease.

Malaria, a mosquito-borne disease caused by a parasite, killed more than 650,000 people in 2010 – most of them children in Africa, according to the World Health Organization.

While several antimalarial drugs have successfully treated the disease, in some regions they no longer work due to drug resistance. Given that just last month the CDC reported that malaria cases in the U.S. reached a 40-year high, this research is particularly timely.

A Global Threat

“Resistance to antimalarial medication threatens the health of more than half of the world’s population,” notes corresponding Paul Roepe, PhD, a Georgetown chemistry professor who authored the study with colleagues at the University of Notre Dame and the University of Kentucky.

Many antimalarial drugs both slow the growth of malarial parasites, and, at higher doses or over longer periods of time, also kill the malarial parasites.

“Until now, no studies have separated how resistance to these two different drug actions might work,” says Roepe, also a professor of biochemistry and cell and molecular biology and co-founder of Georgetown’s Center for Infectious Disease at Georgetown University Medical Center. “Our study found genetic and cell biological evidence linking autophagy to resistance to the parasite, which kills the effects of drugs.”

Important Implications

Autophagy, Roepe explains, is the process by which cells remove damaged parts of themselves to restore normal function. In this case, the cell rids itself of the parts damaged by the antimalarial drug. Roepe worked with two alumni of the chemistry Ph.D. program, David Gaviria (G’13) and Michelle Paguio (G’09), as well as current student Ph.D. chemistry student Amila Siriwardana (G’16) on the research.

The professor and his colleagues demonstrated in their study that while resistance to drugs like chloroquine, which works to slow the growth of malaria, has been explored, an explanation of the resistance to the cell-destroying effects of the medication has not been fully understood.

“These results have important implications in the ongoing development of new antimalarial drug therapy,” Roepe says. “We hope that by publishing this work in an open access journal, more researchers will access it and can expedite drug development.

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HealthMobile – Medical App Built in Africa Launches at Tinapa.

Healthcare delivery around the globe is taking a new technological twist and it is  refreshing to know that Africa is not getting left behind. In this era of smart  devices and high internet connectivity, each of us deserves better access to  healthcare information from the ease of our mobile phones to better manage our  health and make better-informed lifestyle choices. Healthcare data and trends are  a big part of proper personal, social and big healthcare delivery.

The good news is that the much anticipated HealthMobile phone app is now  available for download having launched officially on 21st October at the Tinapa  Business Resort, and the company behind it are set to exceed expectations by  making the content not only global, but personal, social and big.

HealthMobile is the second mobile phone application of the HealthBook Project.  The initiative of creating a cross platform full feature app was founded by Joshua  Ihejiamaizu and Johnson Okorie who are co-owners of NIXIT, the company  directly responsible for managing HealthMobile.

The app in the long term will seek to combine native medical information with  user-generated content to create a top web healthcare facility through which  healthcare delivery can be made possible from any location, with or without the  physical presence of a doctor. The content of the app is also geared towards  helping doctors get smarter and ease the workload attached to their jobs.

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HealthMobile provides Health Topics/Information, Health News focusing on  various categories important to you, Food/Diet information for Lifestyle Planning,  Hospital Locator service for finding the nearest hospital around you,  Drugs/Supplements information, First Aid Information and videos to accompany.

The app is available for Android and BB 10 OS users.

Download the app from the link:
www.nexva.com/31673 or on the Google Play Store as ‘HealthMobile’ for Android
users.

Connect:
Join HealthMobile on Twitter LIVE updates @Health_Mobile

Facebook: www.facebook.com/healthmobile

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Researchers use nanoparticles to deliver vaccines to lungs

CAMBRIDGE, Mass– Many viruses and bacteria infect humans through mucosal surfaces, such as those in the lungs, gastrointestinal tract and reproductive tract. To help fight these pathogens, scientists are working on vaccines that can establish a front line of defense at mucosal surfaces.

Vaccines can be delivered to the lungs via an aerosol spray, but the lungs often clear away the vaccine before it can provoke an immune response. To overcome that, MIT engineers have developed a new type of nanoparticle that protects the vaccine long enough to generate a strong immune response — not only in the lungs, but also in mucosal surfaces far from the vaccination site, such as the gastrointestinal and reproductive tracts.

Such vaccines could help protect against influenza and other respiratory viruses, or prevent sexually transmitted diseases such as HIV, herpes simplex virus and human papilloma virus, says Darrell Irvine, an MIT professor of materials science and engineering and biological engineering and the leader of the research team. He is also exploring use of the particles to deliver cancer vaccines.

“This is a good example of a project where the same technology can be applied in cancer and in infectious disease. It’s a platform technology to deliver a vaccine of interest,” says Irvine, who is a member of MIT’s Koch Institute for Integrative Cancer Research and the Ragon Institute of Massachusetts General Hospital, MIT and Harvard University.

Irvine and colleagues describe the nanoparticle vaccine in the Sept. 25 issue of Science Translational Medicine. Lead authors of the paper are recent PhD recipient Adrienne Li and former MIT postdoc James Moon.

Sturdier vaccines

Only a handful of mucosal vaccines have been approved for human use; the best-known example is the Sabin polio vaccine, which is given orally and absorbed in the digestive tract. There is also a flu vaccine delivered by nasal spray, and mucosal vaccines against cholera, rotavirus and typhoid fever.

To create better ways of delivering such vaccines, Irvine and his colleagues built upon a nanoparticle they developed two years ago. The protein fragments that make up the vaccine are encased in a sphere made of several layers of lipids that are chemically “stapled” to one another, making the particles more durable inside the body.

“It’s like going from a soap bubble to a rubber tire. You have something that’s chemically much more resistant to disassembly,” Irvine says.

This allows the particles to resist disintegration once they reach the lungs. With this sturdier packaging, the protein vaccine remains in the lungs long enough for immune cells lining the surface of the lungs to grab them and deliver them to T cells. Activating T cells is a critical step for the immune system to form a memory of the vaccine particles so it will be primed to respond again during an infection.

Stopping the spread of infection

In studies of mice, the researchers found that HIV or cancer antigens encapsulated in nanoparticles were taken up by immune cells much more successfully than vaccine delivered to the lungs or under the skin without being trapped in nanoparticles.

HIV does not infect mice, so to test the immune response generated by the vaccines, the researchers infected the mice with a version of the vaccinia virus that was engineered to produce the HIV protein delivered by the vaccine.

Mice vaccinated with nanoparticles were able to quickly contain the virus and prevent it from escaping the lungs. Vaccinia virus usually spreads to the ovaries soon after infection, but the researchers found that the vaccinia virus in the ovaries of mice vaccinated with nanoparticles was undetectable, while substantial viral concentrations were found in mice that received other forms of the vaccine.

Mice that received the nanoparticle vaccine lost a small amount of weight after infection but then fully recovered, whereas the viral challenge was 100 percent lethal to mice who received the non-nanoparticle vaccine.

“Giving the vaccine at the mucosal surface in the nanocapsule form allowed us to completely block that systemic infection,” Irvine says.

The researchers also found a strong memory T cell presence at distant mucosal surfaces, including in the digestive and reproductive tracts. “An important caveat is that although immunity at distant mucus membranes following vaccination at one mucosal surface has been seen in humans as well, it’s still being worked out whether the patterns seen in mice are fully reproduced in humans,” Irvine says. “It might be that it’s a different mucosal surface that gets stimulated from the lungs or from oral delivery in humans.”

Tumor defense

The particles also hold promise for delivering cancer vaccines, which stimulate the body’s own immune system to destroy tumors.

To test this, the researchers first implanted the mice with melanoma tumors that were engineered to express ovalbumin, a protein found in egg whites. Three days later, they vaccinated the mice with ovalbumin. They found that mice given the nanoparticle form of the vaccine completely rejected the tumors, while mice given the uncoated vaccine did not.

Further studies need to be done with more challenging tumor models, Irvine says. In the future, tests with vaccines targeted to proteins expressed by cancer cells would be necessary.

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New whole plant therapy shows promise as an effective and economical treatment for malaria

Research by scientists at Worcester Polytechnic Institute and UMass published today in PLOS ONE may point the way toward a new model for malaria treatment that could also be a socioeconomic stimulus for developing nations

 

Worcester, Mass. – In the worldwide battle to curtail malaria, one of the most prevalent and deadly infectious diseases of the developing world, drug after drug has fallen by the wayside as the malaria parasite has become resistant to it. Only artemisinin, derived from the sweet wormwood plant, Artemisia annua, remains as an effective treatment, but it is expensive to produce (particularly when combined with other antimalarial medications to make it less prone to resistance) and is frequently in short supply. Read more

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Researchers pioneer world’s first HIV/AIDS nanomedicines

Scientists at the University of Liverpool are leading a £1.65 million project to produce and test the first nanomedicines for treating HIV/AIDS.

The research project, funded by the Engineering and Physical Sciences Research Council (EPSRC), aims to produce cheaper, more effective medicines which have fewer side effects and are easier to give to newborns and children. Read more

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