Hepatitis B patients who do not respond to lamivudine therapy may benefit from switching to treatment with entecavir according to latest findings published in the July issue of Hepatology. Results indicated that nonresponders to lamivudine therapy had a better virological response after switching to entecavir for a year, and continuing the drug for an additional year led to an even greater clinical improvement without significant side effects.
Worldwide, chronic hepatitis B is the tenth leading cause of death and, while lamivudine is one treatment for HBV, the virus commonly develops resistance to the drug, leading to disease progression. Adefovir dipivoxil is another treatment option, however virologic suppression is not optimal. A third drug, entecavir, has been shown to be a safe and effective treatment for those patients who do not respond to lamivudine.
The research team, led by Morris Sherman of Toronto General Hospital (Toronto, Canada), studied 286 patients taking part in a double-blind, double-dummy, randomized, controlled trial comparing the safety and efficacy of entecavir (1 mg/day) with lamivudine (100 mg/day). The results of the first year of this trial were previously reported and 57% of patients taking entecavir, compared with just 5% of those taking lamivudine, were classified as virologic responders. Those patients were then offered continued therapy for an additional year, after which researchers assessed the efficacy, safety and resistance profile of entecavir through 96 weeks of treatment. “The year-two results demonstrated that patients continue to experience clinical benefit with entecavir therapy beyond 1 year, while the safety profile remained stable,” the authors state.
Further analysis demonstrated that seven patients in the total entecavir-treated cohort had baseline resistance to the drug and another ten became resistant in the first year, with seven more resistant in the second year. “In summary, a second year of entecavir treatment in lamivudine-refractory patients with chronic hepatitis B resulted in continued virologic, serologic and biochemical improvement and a safety profile that was comparable with the first year of therapy,” they conclude.
Source: Sherman M, Yurdaydin C, Simsek H et al. Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical, and serology outcomes through 96 weeks. Hepatology (2008) (Epub ahead of print).
Unveiling HSV1 mechanism offers hope for cold sore sufferers
Scientists at the Duke University Medical Center (NC, USA) have recently demonstrated how herpes simplex virus (HSV)1, the causal virus for cold sores, lies dormant in an inactive phase.
HSV1 lies dormant in the trigeminal nerve of the face until triggered to reawaken by excessive sunlight, fever or other stresses, resulting in cold sores, which have so far evaded a cure, or even a prevention. However, the mechanism that allows the establishment and maintenance of the dormant state remained poorly understood until now.
“We have provided a molecular understanding of how HSV1 hides and then switches back and forth between the latent (hidden) and active phases,” reported researchers led by Brian Cullen. During the inactive phase of HSV1, the virus does not replicate itself and only produces one molecular product, known as latency-associated transcript RNA (LAT RNA). “It has always been a mystery what this product, LAT RNA, does,” Cullen explained. “Usually viral RNAs exist to make proteins that are of use to the virus, but LAT RNA is extremely unstable and does not make any proteins.”
LAT RNA was found to be processed into microRNAs, which block production of the proteins that enable the virus to actively replicate and the virus remains in a dormant state. However, in the event of a larger stress, the virus produces more mRNA than the supply of microRNAs can block, and protein manufacturing begins again, which ultimately leads to the production of proteins that initiate active viral replication. It is believed that cold sores could be treated in the future with a novel combination therapy. “Inactive virus is completely untouchable by any treatment we have. Unless you activate the virus, you can’t kill it,” Cullen revealed. The team is now testing a new drug designed to very precisely bind to the microRNAs that keep the virus dormant. If it works, the virus would become activated and start replicating. Once the virus is active, a patient would then take acyclovir, a drug that effectively kills replicating HSV1. “In principle, you could activate and then kill all of the virus in a patient,” Cullen concluded. “This would completely cure a person, and you would never get another cold sore.”
Source: Umbach JL, Kramer MF, Jurak I, Karnowski HW, Coen DM, Cullen BR. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature (2008) (Epub ahead of print).
NIH grant of US$5.6 million awarded to USU to fight Nipha and Hendra viruses
Researchers at the Uniformed Services University of the Health Sciences (USU) have been awarded a $5.6 million grant from the National Institute of Allergy and Infectious Diseases to develop and test vaccines and treatments for the deadly Nipah and Hendra viruses.
The grant was awarded to continue work on vaccines and therapeutics for Nipah and Hendra led by Christopher Broder of the USU’s Emerging Infectious Diseases program.
In earlier work, Katharine Bossart, a former graduate student in Broder’s laboratory, developed a subunit vaccine for Nipah and Hendra composed of a piece of the virus known as the G glycoprotein.
In other recent studies, Broder’s group, in collaboration with researchers from the National Cancer Institute, developed a potent Nipah and Hendra virus-neutralizing human monoclonal antibody.
“We now have the critical resources needed to evaluate the therapeutic potential of both vaccines and perhaps more importantly a potent human antibody against both Nipah virus and Hendra virus, that could help control outbreaks in geographical regions susceptible to these emerging viruses, and result in a real benefit to those people at risk of infection and disease caused by these deadly agents,” explained Broder.
Source: Medical News Today www.medicalnewstoday.com/articles/113252.php
Hope for avoiding future avian flu pandemics as new DNA vaccine is identified
Scientists at the University of Pennsylvania (PA, USA) have identified a potential new method of vaccinating against avian flu. Researchers immunized experimental animals against various strains of the virus by delivering vaccine via DNA constructed to build antigens against flu, along with a minute electric pulse to ensure increased DNA delivery.
It is hoped that this new approach could allow for the build up of vaccine reserves that could be easily and effectively dispensed in case of an epidemic. “This is the first study to show that a single DNA vaccine can induce protection against strains of pandemic flu in many animal models, including primates,” states author David B. Weiner. “With this type of vaccine, we can generate a single construct of a pandemic flu vaccine that will give much broader protection.”
Traditional vaccines expose a formulation of a specific strain of flu to the body so it can create immune responses against that specific strain. Conversely, a DNA vaccine becomes part of the cell, giving it the blueprint it needs to build antigens that can induce responses that target diverse strains of pandemic flu.
Avian flu is difficult to treat as it mutates quickly, generating different strains that escape an immune response targeted against one single strain.
Preparing effective vaccines for pandemic flu in advance with either live or killed viruses, which protect against only one or a few cross-strains, is therefore very difficult.
In order to overcome this problem, the researchers injected three different species of animal models with synthetic DNA vaccines that are not taken from the flu microbe, but trick the immune system into mounting a broad response against pandemic flu, including strains to which the immune system was never exposed. Antibodies induced by the vaccine rapidly reached protective levels in all three animal species.
“The synthetic DNA vaccines designed in this study customize the antigen to induce more broad immune responses against the pathogen,” Weiner explains.
If proven in humans, this research could lead the way in the preparation against an outbreak of avian flu.
Because these synthetic DNA vaccines are effective against multiple cross-strains, vaccines could be created and stockpiled, prior to a pandemic, and thus be delivered quickly in the event of an outbreak, the authors surmise.
Source: Laddy DJ, Yan J, Kutzler M et al. Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens. PLoS ONE 3(6), e2517 (2008).
New initiatives introduced for rapid diagnosis of drug-resistant TB
Patients from low-resource countries suffering from multidrug-resistant TB (MDR-TB) should now receive a much faster diagnosis and appropriate treatment thanks to two new initiatives unveiled today by the WHO, the Stop TB Partnership, UNITAID and the Foundation for Innovative New Diagnostics.
MDR-TB is a form of TB that responds poorly to standard treatment owing to it’s resistance to the first-line drugs isoniazid and rifampicin. It is currently estimated that only 2% of MDR-TB cases worldwide are being diagnosed and treated appropriately, mainly because of inadequate laboratory services. These new initiatives aim to increase that proportion at least sevenfold over the next 4 years, to 15% or more.
“I am delighted that this initiative will improve both the technology needed to diagnose TB quickly, and increase the availability of drugs to treat highly resistant TB,” said British Prime Minister Gordon Brown.
In developing countries, the majority of TB patients are only tested for MDR-TB if they fail to respond to standard treatments and, even then, it takes 2 months or more to confirm the diagnosis. Patients must wait for the test results before they can receive life-saving second-line drugs and, furthermore, they can infect others with the multidrug-resistant disease.
The new initiative consists of two projects. The first, made possible through US$26.1 million in funding from U-NITAID, will introduce a molecular method to diagnose MDR-TB that was, until now, used exclusively in research settings. These rapid new molecular tests, known as line probe assays, produce a diagnosis in less than 2 days, compared with the standard 2 to 3 months. Under a second, complementary agreement with UNITAID for US$33.7 million, the Global Drug Facility will boost the supply of drugs needed to treat MDR-TB in 54 countries, including those receiving the new diagnostic tests.
“Through the US$60-million support provided by UNITAID, these projects are expected to produce significant results in diagnosing and treating patients as well as reducing drug prices and the costs of diagnosis. These efforts illustrate the way in which innovative financing can be deployed for health and development,” stated Philippe Douste-Blazy, Chairman of UNITAID’s Executive Board.
Source: WHO www.who.int
Diagnostic HYBRIDS awarded grant to monitor drug resistance and vaccine production
Diagnostic HYBRIDS (OH, USA) has received funding through the Biomedical Research Commercialization Program (BRCP) to develop more sensitive and affordable assays to monitor patients infected with HIV and/or HCV and to produce vaccines against influenza virus.
The team will commercialize systems that monitor drug resistance in HIV, HCV and influenza infections and will aid in developing treatments and vaccines for these diseases.
“HIV/AIDS and HCV are two of the most devastating human pathogens of our time, infecting 40 and 180 million people respectively worldwide, and killing a combined 6 million people annually,” stated Miguel Quinones-Mateu, Director of the HIV Program for Diagnostic HYBRIDS.
“Influenza is another deadly disease that is part of the national emerging infectious agent preparedness program. Together, these three viruses cause more deaths than any other agent, disease, or disorder.” He added that “treatment monitoring and vaccine development involving these viral diseases represent a multibillion dollar market opportunity, and this BRCP award cements Ohio’s economic investment and commercialization role in it.”
The researchers are using a yeast-based cloning technology to investigate drug resistance and vaccine development for HIV, HCV and influenza. The methodology will first be commercialized for HIV and future efforts will be directed towards cost-efficient ways to monitor drug resistance and assist in the characterization of new drugs and vaccines for HCV and influenza.
The yeast vector technology platform shows promise for commercialization in national and international markets.
“We are grateful to the Third Frontier Commission for their support of this key initiative,” enthused David R Scholl, Chairman, President & CEO of Diagnostic HYBRIDS. “Our goal has always been to participate in the development of a center of excellence for virology in Ohio. Through our long-term partnership with Case Western Reserve University (OH, USA), we have begun this effort, and the BRCP award will greatly enhance our ability to accomplish this goal in an accelerated fashion,” he concluded.
Source: Medical News Today www.medicalnewstoday.com/articles/113273.php