MALARIA: vaccine could have extra benefits

LILONGWE, 20 June 2011 (IRIN)

 Photo: SAHIMS
Children who received the vaccine are monitored for malaria

The malaria vaccine that has eluded medical science for decades is now within reach, with the final phase of clinical trials underway in seven African countries, including Malawi, where the disease claims 6,500 lives a year, most of them children under the age of five.
Tisungane Mvalo, head of the research team at the Malawian trial site, which is being run in partnership with the University of North Carolina's Institute for Global Health and Infectious Diseases, said the current methods for controlling the incidence of malaria in Malawi have had limited success.
"We have had a moderate reduction in infant mortality from interventions like bed nets and insecticides but malaria remains the leading cause of infant mortality," he said. "There still needs to be an additional intervention."
The multi-country trial of the malaria vaccine RTS,S, made by GlaxoSmithKline Biologicals, is one of the largest ever carried out in sub-Saharan Africa. With funding from GlaxoSmithKline and the PATH Malaria Vaccine Initiative - an NGO that develops research for malaria - 15,000 newborns and infants are being inoculated at 11 sites across the region.
The children are then monitored over a period of 36 months to assess the effectiveness of RTS,S, which in previous studies reduced cases of severe malaria in infants by 53 percent. If the results, due to be released later this, year confirm the vaccine's efficacy in preventing malaria, it could be made available as early as 2015.
"It's a very exciting time," said PATH Director Dr Christian Loucq, speaking from his office in Washington. "We have estimated in our models that a vaccine like this could save hundreds of thousands of lives a year."

The high cost of malaria
A malaria vaccine would not only save lives, it would also alleviate the great burden of the disease on health systems in economically stretched developing countries.
Dr Karl Seydel, a paediatrician at Queen Elizabeth Central Hospital in Blantyre, Malawi, said the impact of the disease on the public health system was "overwhelming" - 5.5 million cases of malaria, equivalent to a third of the country's population, were reported in 2010.
"It drains the resources," he told IRIN. "We could use that money for other things; we could build more hospitals or hire more nurses."
We have estimated...that a vaccine like this could save hundreds of thousands of lives a year
He estimated that during the rainy season, when bites from mosquitoes infected with the malaria parasite are most common, about half of all admissions to the hospital's paediatric ward were due to malaria. The ward was designed for 150 patients but often has to accommodate twice that number.
Malawi has a good track record for immunizing children: 98 percent have received the standard vaccines recommended by the World Health Organization (WHO). The addition of a malaria vaccine, even at 50 percent effectiveness, could greatly reduce the number of children needing expensive hospital care.
Malaria prevention has been less successful than was hoped. According to the 2010 Malawi Demographic and Health Survey, about 70 percent of households have bed nets, but just half the children under five are using them.
Mvalo said the adults in a household often used the nets, even though children are most susceptible to developing severe malaria. In some parts of the country mosquitoes have also started showing resistance to insecticides.
"Each control method has its shortfalls," Mvalo said. "That is why a vaccine is a good alternative - not a replacement, but a good alternative."
Most researchers agree that a malaria vaccine will not substitute for current preventative measures, but could greatly reduce mortality from the disease and create huge financial gains for countries where malaria is endemic. Public health researchers estimate that in such countries, malaria directly absorbs one percent of GDP, excluding indirect costs like loss of work hours.
"Solving the problem of malaria would very much help in terms of economic development," said Loucq.
http://www.irinnews.org/report.aspx?reportID=93024

PATH Malaria Vaccine Initiative to collaborate with GlaxoSmithKline and Crucell in development of second-generation malaria vaccine

Project will combine two promising vaccine approaches to potentially improve immune responses
WASHINGTON, DC, June 7, 2011 — The PATH Malaria Vaccine Initiative (MVI) announced today that it has entered into a collaboration with Dutch biopharmaceutical company Crucell N.V. and GlaxoSmithKline (GSK). This collaboration is aimed at developing a second-generation vaccine against malaria—a deadly disease that kills close to 800,000 people annually, most of them young children under age five in Africa. MVI drives the development of malaria vaccines by joining its scientific, managerial, and field expertise with companies, universities, and governments to test potential malaria vaccines and invest in those with the most promise.
The new project will bring together two promising vaccine approaches in an effort to develop a malaria vaccine that may have the potential to improve on the efficacy of GSK’s first generation RTS,S vaccine candidate. In this collaborative effort, a single dose of Crucell’s weakened recombinant adenovirus Ad35.CS.01malaria vaccine approach will be administered, followed by two doses of GSK’s RTS,S malaria vaccine candidate in a Phase 1/2a clinical trial that is expected to begin later this year. This would be the first test in humans of this “heterologous prime-boost” approach against malaria.
“We are at an important moment in malaria vaccine development,” said Dr. Christian Loucq, director of MVI. “For the first time, we have a malaria vaccine in late phase development in the form of the RTS,S vaccine candidate. This new collaboration, though in the early stages, gives us the opportunity to test an approach with the potential to substantially increase efficacy and move us closer to the internationally agreed upon goal of an 80 percent effective second-generation vaccine by 2025.”
The RTS,S vaccine candidate is currently in the midst of a large-scale Phase 3 clinical efficacy trial. If all goes well in Phase 3 testing, the World Health Organization (WHO) has indicated that a policy recommendation for RTS,S is possible as early as 2015, paving the way for countries to make a decision about implementation through their national immunization programs. The RTS,S trial, which is the outcome of a decade-long collaboration between MVI and GSK, involves 11 sites in seven African countries.
Crucell and MVI first began working together in 2007 to develop adenovirus-based vaccines targeting malaria and are currently collaborating on another heterologous prime-boost approach. Crucell’s Ad35.CS.01 was recently tested in a Phase 1 clinical study in the United States.
RTS,S is a circumsporozoite protein (CSP)-based pre-erythrocytic P. falciparum malaria vaccine candidate that incorporates GSK’s AS01 adjuvant. Crucell’s Ad35.CS.01 vaccine approach uses a weakened, recombinant adenovirus (a type of virus associated with the common cold and other mild respiratory infections) to deliver a malaria antigen to the immune system.
In preclinical studies, the regimen to be evaluated under the new MVI-GSK-Crucell collaboration has shown enhanced immunogenicity when compared to either vaccine candidate given alone.

About the PATH Malaria Vaccine Initiative (MVI)
The PATH Malaria Vaccine Initiative (MVI) is a global program established at PATH in 1999 through an initial grant from the Bill & Melinda Gates Foundation. MVI's mission is to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world. MVI's vision is a world free from malaria. For more information, please visit www.malariavaccine.org.

About PATH
PATH is an international nonprofit organization that creates sustainable, culturally relevant solutions, enabling communities worldwide to break longstanding cycles of poor health. By collaborating with diverse public- and private-sector partners, PATH helps provide appropriate health technologies and vital strategies that change the way people think and act. PATH’s work improves global health and well-being. For more information, please visit www.path.org.

MALARIA: Could malaria vaccine “sit on the shelf”?

13 Dec 2010 : Paul Chinnock
By the year 2015, the first vaccine against malaria could be ready for use on a wide scale. But concerns have been expressed that inadequate planning could prevent it reaching those who are most in need of protection against the disease.
Of several potential malaria vaccines under investigation, the RTS,S vaccine is at the most advanced stage. Its history dates back to research conducted by GlaxoSmithKline and the Walter Reed Army Institute of Research in the mid-1980s. The first human trials began a decade later. A partnership between GSK and the non-profit PATH Malaria Vaccine Initiative (MVI) has made possible its further development.
Phase 3 clinical trials in sub-Saharan Africa began in 2009. Eleven sites in seven countries will enrol a total of 16,000 infants and children. Steps have been taken to expedite the rapid approval of the vaccine by African regulatory authorities, as well as by officials at WHO and the European Medicines Agency, assuming that the trials confirm the effectiveness and safety of RTS,S. It is hoped that this will lead on to the vaccine entering general use as early as 2015.
The level of effectiveness of the vaccine will not be clear until the Phase 3 trials have been completed. It is already apparent that it will not be as effective as vaccines for many other diseases, but a Phase 2 trial in Tanzania [1] found that RTS,S reduced the risk of Plasmodium falciparum infection by 65% and this degree of effectiveness (or even lower) could still save many lives each year. Malaria control programmes would use the vaccine in combination with other tools – residual insecticide spraying of houses, long-acting insecticide-treated bednets, rapid diagnostic tests, and treatment using artemisinin combination therapy.
But the fear of many malaria specialists is that, once the vaccine is ready, health systems in malaria-endemic countries may not be able to bring it into use, because of inadequate preparation. “After decades of research and tens of millions of dollars invested … it would be scandalous if this vaccine just sits on the shelf,” said Yvette Collymore of MVI speaking at a recent conference in Washington DC, USA.
The concern expressed by MVI raises a wider issue. In recent years – with new funding, from sources such as the Gates Foundation and the establishment of a number of public–private product development partnerships – we have seen more R&D efforts targeted on the infectious diseases of poverty. An encouraging number of new tools are now in the development pipeline. But R&D is only the beginning. It will be essential that systems are in place to put the new tools to work and make them available to all those who need them.

Reference
Abdulla S, Oberholzer R, Juma O, Kubhoja S, Machera F et al. (2008). Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med; 359(24):2533-2544. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19064623

http://www.tropika.net/svc/news/20101213/Chinnock-20101213-News-RTSS

MALARIA: PATH Malaria Vaccine Initiative

December 14, 2010
Development of a vaccine to prevent the malaria parasite from entering the human liver is the goal of a new collaboration announced today by global leaders in malaria research and vaccine development. The PATH Malaria Vaccine Initiative (MVI), Merck (known outside the US and Canada as MSD), and NYU Langone Medical Center are working together to evaluate an approach targeting a novel part of a major surface protein on the malaria parasite. Malaria is estimated to kill close to 900,000 people each year with the majority of deaths occurring in children under the age of five in sub-Saharan Africa.
The circumsporozoite protein (CSP) has been recognized as a potential target in the development of vaccines focused on the earlier stages of malaria infection. The researchers working on this project are focusing on a new approach that targets a region of CSP important to a critical function of the protein. By blocking this function, it is hoped that invasion of the parasite into the liver, an essential step in causing malaria disease, can be prevented.
“We think we can improve the way sub-unit vaccines are designed by strategically targeting this critical protein function,” noted Dr. Elizabeth Nardin, professor in the Department of Medical Parasitology at NYU Langone Medical Center. “Other vaccine approaches targeting CSP have required extremely high levels of antibody, which are difficult to elicit and to maintain. This approach has the potential to address that problem.”
The rationale for pursuing this targeted “peptide protein conjugate” approach is based on knowledge of both the vaccine technology to be used and the targeting of a particular malaria protein known to elicit an immune response. CSP has already been shown to have significant protective efficacy in the field, in the context of RTS,S, the most advanced malaria vaccine candidate, now in a Phase 3 clinical trial. Additionally, other conjugate based vaccines developed against bacterial pathogens have been incorporated into licensed, widely used pediatric vaccines by Merck.
“History has shown that vaccines can be a powerful tool against disease,” said Dr. John Shiver, vice president of vaccines discovery at Merck. “We recognize that new methods and partnerships, like this collaboration with MVI and NYU Langone Medical Center, are important to continue innovation in the battle against the malaria parasite.”
“With the availability of a first-generation malaria vaccine on the horizon, we are ramping up our efforts to seek out and invest in scientific approaches for malaria vaccines that could potentially be even more effective and protect more people,” said Dr. Christian Loucq, director of MVI. “We are very pleased that one of the world’s largest pharmaceutical companies and a major academic medical center have committed to testing a promising new way to defend children against malaria.”
Although this vaccine approach is being tested primarily for use in children younger than one year of age, it could be used to help prevent disease in all populations vulnerable to Plasmodium falciparum, the most deadly species of the parasite, and could potentially be adapted to prevent P. vivax as well. Approximately 40 percent of the world’s population lives at risk of contracting malaria caused by P. vivax and/or P. falciparum.
“Though it is quite early, we are excited to have the opportunity to explore the promise of this innovative vaccine approach with Merck and MVI,” said Dr. Photini Sinnis, associate professor in Medical Parasitology at NYU Langone Medical Center.
###
The PATH Malaria Vaccine Initiative (MVI) is a global program established at PATH in 1999 through an initial grant from the Bill & Melinda Gates Foundation. MVI's mission is to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world. MVI's vision is a world free from malaria.
 www.malariavaccine.org.

MALARIA: Roll back Malaria

PROGRESS & IMPACT SERIES Number 3 . September 2010
Saving Lives with Malaria Control:
Counting Down to the Millennium Development Goals
New Report shows investment in malaria prevention paying off: hundreds of thousands of children’s lives saved
Model predicts more good news: with increased funding, another 3 million deaths can be prevented

A new report confirms that the current global investment in malaria control is saving lives and that further increases in funding will contribute significantly to achieving the Millennium Development Goals (MDGs) for health. Saving Lives with Malaria Control: Counting Down to the Millennium Development Goals – authored by Tulane University, Johns Hopkins University, WHO and PATH and published today by the Roll Back Malaria Partnership (RBM)– reveals that the lives of almost three quarters of a million children in 34 African countries are estimated to have been saved in the past 10 years, through the use of insecticide treated mosquito nets, indoor residual spraying, and preventive treatment of malaria during pregnancy.
The report estimates that an additional 3 million lives could be saved by 2015 if the world continues to increase investment in tackling the disease.
Malaria causes over 850,000 deaths per year worldwide, the majority of deaths in Africa where the disease accounts for almost 20% of all child deaths. Malaria also threatens the health of pregnant women. In sub-Saharan Africa , as many as 10,000 pregnant women die each year of malaria-related causes, mainly anaemia.
Massive increases in the availability of insecticide treated nets have been recorded in the last few years. However, directly measuring the impact of insecticide nets, treatments and other malaria control efforts is difficult as health information systems remain weak, and the majority of malaria deaths are not properly recorded.
The Lives Saved Tool (LiST) - developed to be used across major childhood diseases - is being applied to malaria prevention across Africa . The report provides the first assessment of lives saved based on the level of coverage achieved with currently available malaria prevention tools. Although this does not include data on lives saved from diagnosis and treatment, and is likely to be an underestimate, the results show just how much progress has been made.
"The findings from this report clearly show the efficacy of our efforts to save lives, especially among children in Africa ," says Professor Awa Coll Seck, RBM Partnership Executive Director. "This is a vital tool which can help strengthen country planning and guide us all as we focus on 2015." Findings from the report also show that the number of rural households protected by either insecticide-treated nets or indoor residual spraying has increased significantly, especially in the latter half of this decade. The report estimates that malaria funding in 2010 could result in 500 more children alive every day.
"This report demonstrates the critical importance of malaria control efforts to reaching the healthrelated Millennium Development Goals by 2015" states Dr Robert Newman, director of the Global Malaria Programme at WHO. "Without continued investment in malaria, reaching the MDG for child survival is unlikely to be reached in Africa ."
"While we've made great progress, much work remains", said Rear Admiral (Ret.) Tim Ziemer, U.S. Global Malaria Coordinator. "To reach the Millennium Development Goals, we must accelerate our efforts to expand not only malaria prevention and treatment, but also a broad range of communitybased health services. The Administration's Global Health Initiative is helping partner countries achieve major advances through innovation, integration and improved health service delivery in countries."
Progress made in controlling malaria is still very fragile. The Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest funder of malaria control programmes worldwide, will hold its third replenishment meeting in November 2010, where governments will make financial pledges which may well determine if the malaria-related MDGs can be achieved.
http://www.rollbackmalaria.org/ProgressImpactSeries/docs/report3-en.pdf

BIOTERRORISM: Swine flu yielded valuable lessons for future

Carol Campbell and Yojana Sharma
25 August 2010
The pandemic scare highlighted the global shortage of vaccine
As the WHO declared the end of the swine flu pandemic earlier this month, the high financial cost incurred in preparing defences against the disease has left many countries wondering whether it was money that could have been better spent, given that the disease failed to spread as widely as feared.
But experts say that while the cost of vaccines and anti-virals was high, the lessons learned and the monitoring systems put in place will protect humanity from inevitable future virus outbreaks.
Frew Benson, South Africa's chief director of communicable diseases, said the country spent 115 million rand (US$15.6 million) on vaccine but has only used about US$3.4 million worth. The remaining vaccine will, until it expires, remain part of the country's strategic stock against the epidemic, Benson said.
There also remains a huge stockpile of antivirals. Benson said 100,000 courses were imported for South Africa but only 25,000 have been used so far. The cost of wasted expired vaccine and antivirals will be shouldered by purchasing governments.
"This country was lucky, for some reason this epidemic didn't hit us as hard as other countries in Africa. West Africa is battling far more with A(H1N1) than we are here," said Benson.
Lucille Blumberg, head of epidemiology at South Africa's National Institute for Communicable Diseases, said it was not all wasted — laboratories had been upgraded and skills improved across Africa to cope with the epidemic.
"Yes, there was excessive use of resources in South Africa during the epidemic," she told SciDev.Net. "But this was inevitable."
"There was a time, at the height of the epidemic, when laboratories couldn't cope," she said. "In hindsight we didn't need to test and treat every case, but at that stage we didn't know what we were dealing with — or how dangerous it was."
Rick Bright, scientific director of the global vaccine development programme at Seattle-based nongovernmental organisation PATH, said that a network of influenza centres around the world had been strengthened and regional labs expanded, including in Africa where there are now major laboratories in Madagascar, Senegal and South Africa.
This is particularly important for flu, which does not display specific external symptoms and can be diagnosed only through laboratory testing.
"H1N1 taught us a lot by intensifying attention without the occurrence of fatalities. It was a dry-run for a larger more lethal flu pandemic," said Bright, who has been reviewing the needs of low-income countries for the Influenza VII conference, to be held in Hong Kong in September.
He said the pandemic scare highlighted the global shortage of vaccine, and the need for countries to be able to manufacture antivirals and vaccines within their own countries.
"Stockpiling is not a solution, because no one knows what the next mutation of the influenza virus will be," Bright said.
"Maintaining a stockpile has major costs and you have to continually test the vaccine for potency and that also has costs," said Kathleen Neuzil, Senior Advisor for Immunizations at PATH. The H5N1 vaccine, for example, is more stable in bulk form, but once it is in syringes and vials it can lose its potency within a year.
"The emergence of H1N1 showed the limitations of a stockpile concept, particularly for low-income countries," said Katherine Neuzil, director of PATH's global vaccine work. "You don't have time to put in place a stockpile if the virus mutates."
"In terms of preparedness, we are in much better shape than ten, five, or even two years ago, especially in terms of the degree of surveillance, and the number of countries involved in surveillance," Neuzil said.
http://www.scidev.net/en/news/swine-flu-yielded-valuable-lessons-for-future-say-experts.html