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Better Vaccines for Tuberculosis Could Save Millions of Lives

ScienceDaily (Aug. 28, 2012) Cases of one of the world's deadliest diseasestuberculosisare rising at an alarming rate, despite widespread vaccination. Reasons for the ineffectiveness of the vaccine, especially in regions where this infectious disease is endemic, as well as arguments for replacing the existing vaccine with novel synthetic vaccines, are presented in a review published online August 28th in Trends in Molecular Medicine.

"Tuberculosis is a global health threat, and it is a highly communicable disease that may influence practically anyone and everyone," says senior author Javed Agrewala of the CSIR-Institute of Microbial Technology in Chandigarh, India. "There is a serious need and challenge for the scientific community to develop alternative vaccination approaches for the control of the disease." Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis (Mtb). About one third of the world's population is infected with Mtb, which causes about two million deaths each year. Vaccines may be the best strategy for controlling tuberculosis, but the only available vaccineBacillus Calmette-Guerin (BCG)does not reliably prevent the disease in adults, especially in regions where tuberculosis is endemic. In the review, Agrewala explains that BCG does not work well in these regions because exposure to prevalent mycobacterial strains triggers the production of antibodies that counteract the vaccine. In addition, infections with parasitic worms called helminths interfere with protective immune responses induced by BCG. To overcome these limitations, Agrewala proposes the use of novel vaccines called lipidated-promiscuouspeptide vaccines. These synthetic vaccines are safer than BCG because they do not contain infectious material. Moreover, they generate long-lasting, protective immune responses and are not influenced by preexisting antibodies. This type of vaccine strategy has already proven to be successful in an animal model of tuberculosis and is being tested in human clinical trials for other infectious diseases and cancer. "We believe that lipidated-promiscuous-peptide vaccines have all the essential qualities that can make them successful in tuberculosis-endemic countries," Agrewala says. "Such vaccines can impart better protection than BCG and will have a long-reaching positive impact on millions of people."

Gowthama et al. "Lipidated promiscuous peptides vaccine for tuberculosis-endemic regions" Cell Press (2012, August 28). Better vaccines for tuberculosis could save millions of lives. ScienceDaily. Retrieved August 30, 2012, from http://www.sciencedaily.com /releases/2012/08/120828134936.htm

Compound Discovered That Boosts Effect of Vaccines Against HIV and Flu
ScienceDaily (Aug. 26, 2012) Oxford University scientists have discovered a compound that greatly boosts the effect of vaccines against viruses like flu, HIV and herpes in mice.

An 'adjuvant' is a substance added to a vaccine to enhance the immune response and offer better protection against infection. The Oxford University team, along with Swedish and US colleagues, have shown that a type of polymer called polyethyleneimine (PEI) is a potent adjuvant for test vaccines against HIV, flu and herpes when given in mice. The researchers were part-funded by the UK Medical Research Council and report their findings in the journal Nature Biotechnology. Mice given a single dose of a flu vaccine including PEI via a nasal droplet were completely protected against a lethal dose of flu. This was a marked improvement over mice given the flu vaccine without an adjuvant or in formulations with other adjuvants. The Oxford researchers now intend to test the PEI adjuvant in ferrets, a better animal model for studying flu. They also want to understand how long the protection lasts for. It is likely to be a couple of years before a flu vaccine using the adjuvant could be tested in clinical trials in humans, the researchers say. 'Gaining complete protection against flu from just one immunisation is pretty unheard of, even in a study in mice,' says Professor Quentin Sattentau of the Dunn School of Pathology at Oxford University, who led the work. 'This gives us confidence that PEI has the potential to be a potent adjuvant for vaccines against viruses like flu or HIV, though there are many steps ahead if it is ever to be used in humans.' HIV, flu and herpes are some of the most difficult targets to develop vaccines against. HIV and flu viruses are able to change and evolve to escape immune responses stimulated by vaccines. There aren't any effective vaccines against HIV and herpes as yet, and the flu vaccine needs reformulating each year and doesn't offer complete protection to everyone who receives it. Finding better adjuvants could help in developing more effective vaccines against these diseases. Most vaccines include an adjuvant. The main ingredient of the vaccine -- whether it is a dead or disabled pathogen, or just a part of the virus or bacteria causing the disease -primes the body's immune system so it knows what to attack in case of infection. But the adjuvant is needed as well to stimulate this process.

While the need for adjuvants in vaccines has been recognised for nearly 100 years, the way adjuvants work has only recently been understood. The result has been that only a small set of adjuvants is used in current vaccines, often for historical reasons. The most common adjuvant by far is alum, an aluminium-containing compound that has been given in many different vaccines worldwide for decades. However, alum is not the most potent adjuvant for many vaccine designs. 'There is a need to develop new adjuvants to get the most appropriate immune response from vaccines,' says Professor Sattentau, who is also a James Martin Senior Fellow at the Oxford Martin School, University of Oxford. The Oxford University team found that PEI, a standard polymer often used in genetic and cell biology, has strong adjuvant activity. When included in a vaccine with a protein from HIV, flu or herpes virus, mice subsequently mounted a strong immune response against that virus. The immune response was stronger than with other adjuvants that are currently being investigated. The team also showed that PEI is a potent adjuvant in rabbits, showing the effect is not just specific to mice and could be general. Another potential advantage of PEI is that it works well as an adjuvant for 'mucosal vaccines'. These vaccines are taken up the nose or in the mouth and absorbed through the mucus-lined tissues there, getting rid of any pain and anxiety from a needle. Mucosal vaccines may also be better in some ways as mucosal tissues are the sites of infection for these diseases (airways for respiratory diseases, genital mucosa for HIV and herpes). Professor Sattentau suggests that: 'In the best of all possible worlds, you could imagine people would have one dose of flu vaccine that they'd just sniff up their nose or put under their tongue. And that would be it: no injections and they'd be protected from flu for a number of years. 'It's just a vision for the future at the moment, but this promising adjuvant suggests it is a vision that is at least possible.' University of Oxford (2012, August 26). Compound discovered that boosts effect of vaccines against HIV and flu. ScienceDaily. Retrieved August 30, 2012, from http://www.sciencedaily.com /releases/2012/08/120826143537.htm

Hyperbaric Oxygen Could Provide Relief of Chronic Pain

ScienceDaily (Apr. 22, 2012) Chronic pain affects about 76 million people in the U.S. and carries an economic burden of nearly $100 billion annually. The most frequently used medications, narcotic and non-narcotic analgesic drugs (e.g., morphine, ibuprofen, etc.), do not provide complete or sustained relief of chronic pain. Scientists are currently seeking alternative solutions for chronic pain management.

One possible solution is hyperbaric oxygen (HBO2) therapy, which is the clinical application of pure oxygen at higher-than-atmospheric pressure for limited time periods to achieve beneficial results. The FDA has approved HBO2 treatment for certain conditions such as decompression sickness (the 'bends') and carbon monoxide poisoning but not for pain specifically. Yangmiao Zhang, a graduate student in the laboratory of Raymond M. Quock, Ph.D., Professor of Pharmaceutical Sciences at Washington State University, evaluated whether relief of neuropathic pain could be enhanced by increasing the number of HBO2 treatments. Male rats were injected and tested on their paws for pain thresholds at four different times. Twenty-four hours after the last injection, rats were treated with a 60minute period of room air (the control), or HBO2. Rats that underwent the most number of HBO2 treatments (four 60-minute treatments) recovered approximately 7 days earlier than rats who received a single treatment. Quock concluded, "While most other HBO2 pain studies focus on inflammatory mechanisms, we believe that HBO2 also reduces pain by acting in the brain. Studying the mechanism of how HBO2 can reduce neuropathic pain can reveal molecular targets in the brain and possibly stimulate the development of new drugs that act on the same targets for long-term relief of chronic pain." This research was supported by Washington State University. Federation of American Societies for Experimental Biology (FASEB) (2012, April 22). Hyperbaric oxygen could provide relief of chronic pain. ScienceDaily. Retrieved August 30, 2012, from http://www.sciencedaily.com /releases/2012/04/120422162210.htm

Little Benefit of Breast Imaging Tests for Women With Breast Pain, Study Suggests

ScienceDaily (Mar. 7, 2012) Researchers from Boston University School of Medicine (BUSM) and Boston Medical Center (BMC) have found that women with breast pain who receive imaging (mammograms, MRIs or ultrasounds) as part of breast pain evaluation, undergo follow-up diagnostic testing, but do not gain benefit from these additional studies. These findings currently appear on-line in Journal of General Internal Medicine.

Breast pain is a common breast health complaint, but very few women with breast pain alone have an underlying breast cancer. The guidelines for management of women with breast pain are not clear, though past studies have suggested that other tests beyond the routine screening mammogram can provide reassurance for women with breast pain. The researchers analyzed a group of 916 women who were referred from 2006-2009 for breast pain at Boston Medical Center. They compared the clinical management of women who received imaging to evaluate breast pain to women who did not. Six cancers were identified: all these women either had a lump on exam, or had a routine screening mammogram find a cancer in the other breast. For women who had a completely normal breast examination, the addition of an ultrasound, MRI or mammogram did not help the patient or the doctor in their decisions. The additional ultrasounds and other studies beyond the regular screening mammogram did have a potential negative side, including additional doctor visits, more mammograms and other tests as well as more biopsies. "While some have suggested that doing further testing in women with breast pain will help to reassure the patient, we did not find this to be the case," explained lead author Mary Beth Howard, MS, an MD candidate, BUSM Class of 2015. Howard authored this study under the mentorship of Drs. Karen Freund, Tracy Battaglia and Marianne Prout of the Women's Health Unit in the Department of Medicine at BUSM and BMC. "More tests are not always a good thing. They can lead to still further tests or even biopsies which themselves have some risk. They can sometimes increase anxiety without providing any benefit to the patient," she added. According to the researchers, if the goal is to improve health care quality, it is important to determine if imaging in women with breast pain is a valuable diagnostic tool. "We hope this study is a first step in providing better direction for managing women with breast pain, and hopefully emphasizing that additional imaging studies are not indicated in women unless there is a focal breast complaint, such as a mass or lump," said Howard. Boston University Medical Center (2012, March 7). Little benefit of breast imaging tests for women with breast pain, study suggests. ScienceDaily. Retrieved August 30, 2012, from http://www.sciencedaily.com /releases/2012/03/120307094612.htm

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