RTS,S/AS01E is one of several potential vaccines under development that target the pre-erythrocytic stage of the disease engineered using genes from the outer protein of Plasmodium falciparum malaria parasite and a portion of a hepatitis B virus with a liposomal chemical adjuvant to boost the immune system response.

Malaria: A dreaded disease

Malaria is caused by a parasite carried in the saliva of mosquitoes and is endemic in more than 100 countries worldwide. As per the 2012 WHO fact sheet, malaria is a preventable and treatable mosquito-borne disease, whose main victims are children under five years of age in Africa. According to the latest WHO estimates, there were about 219 million cases of malaria in 2010 and an estimated 660,000 deaths. Africa is the most affected continent with about 90% of all malaria deaths. Pregnant women and their unborn children are particularly vulnerable to the disease.

Why vaccine?

The current war against malaria is fought with a variety of weapons, including the distribution of bednets, the promotion of indoor spraying, and the development of new medicines and insecticides. Deployment of these lethal weapons has been plagued with a variety of challenges ranging from lower manufacturing capacities for bednets, inefficient distribution channels, and parasites/mosquito’s resistance to drugs and insecticides. A vaccine is been developed to bridge these gaps. Even a modestly efficacious malaria vaccine would be very handy.

So far, vaccines have been developed by three main approaches: a) those targeting pre-erythrocytic stage of the parasite. b) those targeting the blood stage of the parasite and c) those interrupting the life cycle of the parasite by inducing antibodies that prevent the parasite from maturing in the mosquito. Elaborate spreadsheet is available in what is known as the ‘Rainbow table’ put together by WHO.

Vaccine story so far:

RTS,S was developed in the late 1980s by researchers at GlaxoSmithKline Biologicals in Rixensart, Belgium, and later in partnership with the PATH Malaria Vaccine Initiative. Work on the RTS,S vaccine began a quarter of a century ago within the US military, with development since 2001 being carried out by a public–private venture between the PATH Malaria Vaccine Initiative (MVI) – supported by the Bill & Melinda Gates Foundation and the pharma giant GlaxoSmithKline. Early results from larger, ongoing phase III trials have shown that the vaccine cut malaria cases to half during the first year of follow up in young children, and by about a third in babies. In November 2012, results from phase III tests on 6,500 infants showed that the RTS,S vaccine only protected about a third of infants, compared to success rates of between 47 percent and 55 percent in children between the ages of five and 17 months. This is also a matter of concern as the youngest age groups are most prone to the disease!

Recent Phase II results: A damp squib?

The latest setback is reported from a phase II follow-up study on 320 children in Kilifi, Kenya which found that in the first year after vaccination, protection against malaria was 43.6 percent, which dropped to zero by the fourth year. It was also found that the more often a child was exposed to malaria, the less effective the vaccine appeared to be. Briefly, the study showed that the vaccine’s efficacy was 45.1 percent in children with below-average exposure to malaria, and just 15.9 percent in children with above-average exposure. Interestingly, it was also found that for every 100 vaccinated children, 65 cases of clinical malaria were averted.

This study that began in 2009, with an objective to assess safety and efficacy ahead of the large-scale phase III trials involved 447 children, out of which 320 were able to be followed up for four years.

What’s in store?

Reportedly, Mary Anne Rhyne, the US spokesperson from GlaxoSmithKline, was of the opinion that the Kenya study is small and uses data from just one of many trial sites, while larger studies are still under way. According to her, the ongoing phase III pivotal study, involving 15,460 children should provide meaningful insights into the vaccine candidate’s efficacy in different malaria parasite transmission settings, longer-term efficacy (2.5 years after primary vaccination) and the impact of a booster dose. The results for these studies are expected by the end of 2014.

As per the reports, the researchers of the study, although disappointed, have not lost hope and believe that a booster dose could help pep up the response to the disease. This phenomenon is not unheard of in vaccine clinical use.

A glimmer of hope after all:

While researchers in Africa and elsewhere were grappling to come to terms with these results, path breaking progress was being made elsewhere. A prolific group of researchers from parts of US, Australia, Europe and Asia reported in their article published in Science Translational Medicine, discovery of a new compound ELQ-300 (chemical class: The 4(1H)-quinolone-3-diarylethers). ELQ-300 works by interrupting the lifecycle of Plasmodium, whereby it disables the power house aka mitochondria of Plasmodium cells. The parasite is thus destroyed, and a person does not experience symptoms. The researchers claim that ELQ-300 also prevents transmission since a person who has taken ELQ-300 no longer has active Plasmodium in their bloodstream. As per some of the reports that I went through, this drug is been tipped as the next big thing in the war against malaria. As per my analysis, most antimalarial drugs are high dosed and need frequent administration due to their poor bioavailability. Here’s a catch-22, food improves the bioavailability of these drugs but one of the side effects of these drugs is nausea and vomiting, thereby hindering food intake in patients. In their pre-clinical studies in mice, ELQ-300 has shown good bioavailability, metabolic stability and efficacy. Still early days for ELQ-300, but definitely promising!

Meanwhile, reportedly around the same time, another group based out of New Delhi, India took a great leap forward in their exciting search for an elusive malarial vaccine. The results published in The American Society for Microbiology-Infection and Immunity, pointed towards identification of three key parasite antigens that elicited potent inhibition against Plasmodium Falciparum strains. Going by the preclinical results, this could very well be a potent weapon in the arsenal against malaria!

With today being world Malaria day what could possibly be of more importance!?

-Shankar Swaminathan

As you may know, NANOMED2020 is a Coordination and Support Action under the FP7-Health which started in September 2012 for a total duration of 18 months, involving seven partners across Europe including the ETP Nanomedicine (more information about NanoMed 2020 is to be found on the ETPN website at: http://www.etp-nanomedicine.eu/nanomed2020/public)

It is a unique opportunity to deliver concrete recommendations to the European Commission to push forward the field of nanomedicine under Horizon 2020 and to propose concrete actions to bring more nanomedicine products on the market via a value chain optimisation.

Amongst other activities, NANOMED2020 is currently focusing on:

• Identifying the key bottlenecks of the value chain to focus on to leverage the translational possibilities of the development process
• Federating the nanomedicine community and establishing a European landscape via mapping all relevant actors, projects and infrastructures.

The first results of such exhaustive mapping have come out after a first-phase consolidation, focusing on industrial players and SMEs. Overall more than 800 companies have been listed with potential interest and 500 with a more direct link/activity to nanomedicine.

In parallel, and to consolidate the nanomedicine landscape, a 10 minutes online questionnaire has been designed and approved to gather additional data and to deliver first insights into the main gaps and needs of the nanomedicine value chain.

All stakeholders (including academia, SMEs, large and pharmaceutical industries, research institutes, CROs, CMOs, characterisation centres) and fields of expertise (including drug delivery and regenerative medicine but not cosmetics),  are invited to take part in this survey, as we hope to gather inputs from the whole nanomedicine community.

The overall resulting landscape will be a unique and tremendously powerful tool to stress the dynamism of the field and the importance to bring nanomedicine upfront at the European level.
Individual actors listed in the mapping would hence benefit of an increased visibility at the European level and of future matchmaking opportunities.

Please access the questionnaire here and be sure to take part in this worldwide mapping of nanomedicine actors and activities:

https://www.vdivde-it.de/mrIWeb/mrIWeb.dll?I.Project=NANOMED2020&goback=.gmr_2520319.gde_2520319_member_217746248

I stay at your disposal for any question you may have and would like to thank you in advance for your coming contribution in this important action. – Olivier Fontaine

Olivier is trained as a multidisciplinary engineer at Ecole Centrale de Lille (France) and finalized in September 2012 a double degree program at Cranfield University (UK) with a Nanomedicine MSc. His MSc thesis on the nanomedicine commercial landscape and co-supervised by Dr Bojan Boskovic from Cambridge Nanomaterials Technology Ltd allowed him to gain advanced knowledge, skills and practical experience in the identification and understanding of drivers, needs and players in the supply chain of nanomedicine.

Building upon his expertise, Olivier Fontaine is now working at the secretariat of the European Technology Platform on Nanomedicine (ETPN, Germany) as an International Volunteer from Nanobiotix (France). Taking an active role in the NanoMed 2020 European project and in the elaboration of strategic documents, he is currently in charge of mapping the nanomedicine actors and initiatives at the European level, along with contributing to novel communication tools and establishing the state-of-the art activities and needs in translational nanomedicine.

You can find Olivier on LinkedIn.

We are delighted to welcome Dr Shankar Swaminathan, Ph.D. as a new guest blogger here at medicalnanotec.com. Dr. Swaminathan is curently a Post-Doctoral research fellow at the Hamilton Eye Institute, University of Tennessee.

• In a nutshell, Dr. Swaminathan is a pharmaceutical scientist and polymer chemist turned into an eye/vision researcher.  Dr. Swaminathan received his Ph.D. in Pharmaceutics from the Institute of Chemical Technology, Mumbai, India. He was also a research assistant at the University of Turin, Italy during his Ph.D. He went on to gain research experience in the industry after his Ph.D. specializing in long acting polymeric medical devices for contraception where he was instrumental in getting the product to the scale up stage. He then decided to fortify his repertoire further by gaining postdoctoral research experience in the US in eye/vision research.
• Currently, a postdoctoral researcher at the University of Tennessee Health Science Center. His research revolves around studying genetic modifiers of glaucoma with a special emphasis on intraocular pressure and developing personalized nanomedicine. Research involves gene mining using bioinformatics tools and systems genetics. He is also a part of the team developing novel nano-therapies for dry age related macular degeneration.
• Pioneered the work on Nanosponge synthesis and applications in drug delivery.
• Over the years, contributed towards research in drug delivery technology, nanotechnology, ocular drug delivery, ocular pharmacokinetics, systems biology, bioinformatics, solublization of drug actives, medical devices, etc.
• General research interests revolve around providing value added medicine to alleviate diseases by applying polymeric nanoparticle technology, controlled drug delivery, solubilization, cyclodextrin based drug delivery systems, ocular pharmacokinetics and biodistribution. Solid dispersion, drug/particle/pellet coating, pellets into tablet technology, Silicone based controlled release medical devices for contraception, Intrauterine medical devices, anticancer drug therapy optimization by solubilization and bioavailability enhancement, stabilization of macrocmolecules/proteins by use of nanosponge technology, physicochemical stabilization of molecules.
• He is also interested in the commercial aspects of research dealing with bench to market transition of a product, and product licensing. He has keen interest in the FDA regulations and IP related issues pertaining to product filings.

To find out more about Dr. Swaminathan

This study brings hope for using nanoparticulate detectors for cancerous lesions, which would be a great step forward for early detection of cancer. It is important to perform nano-toxicological experiments as the safety of administering these interventions is one of the most important concerns that needs to be addressed before any Nanotechnology can be administered to humans. This study shows promising results indicating that this may be a viable pathway to enhance cancer detection at the cellular level.

It is assumed that a cellular detection of cancerous cells would allow for swifter clinical intervention into the disease. Thus allowing a reduction in the subsequent mortality associated with the disease. As of course with most cancers the early they are found and treated the more likely a person is to survive.

-CT

Article: Stanford

The 2011 programme will cover:

• The future impact of nanotechnology on business and the economy
• Expert analysis of the global market and trade environment
• International success stories in fostering nanomaterials development
• What major global end users need from their supply base
• Lessons learned from commercialising R&D in this sector
• How to manage innovation and deliver on commercial potential
• How to sell nanomaterials in the consumer marketplace
• Policy and legal frameworks for producers in this sector
• Capital investment, funding and trading mechanisms
• Innovations in production and synthesis of nanomaterials
• Novel applications in coatings, plastics, composites, electronics, medicine, and clean technology

NanoMaterials 2011 will bring an even larger exhibition of leading suppliers and products with extensive networking opportunities.

The conference NanoMaterials conference and exhibition will take place on 8-9 June.

For more information visit: nanomaterials-conference.com

Queue the new findings of the Chilkoti lab at Duke University who have demonstrated that adding a poly(ethylynglycol) (PEG) chain by polymerisation to the protein drug can increase the retention of said protein in the blood. It does this by effectively increasing the proteins hydrodynamic radius making the drug bigger and therefore easier to be retained in the blood.

This new polymerisation approach of Chilkoti has overcome many previous problems of PEGylation of drugs such as problems with PEG length and placement of the polymer.

A common disease treated by protein drugs is cancers as they have leaky vessels and are therefore easy targets for these drugs. However previously the protein drugs had such short lifetimes in the blood they couldn’t accumualte efficiently in the tumours. Now with the edition of up to 20nm PEG tails Chilkoti has shown a far better drug efficiency and effect.

This is another scenario whereby the application of nanotechnology has come to the aid of medical science to overcome problems with existing techniques of drug delivery and effectiveness. – CT

Sources : Chilkoti et.al.; Nature

Image: Human breast cancer cell tagged with quantum dots

Cancer Nanomedicine is developing to cover a wide range of applications from imaging, diagnosing to treating cancers with targeted therapies. Cancer Nanomedicine works on the theory that nanometer sized particles of gold, nanomicelles and quantum dots (QDs) have unique functional properties that differ from other available discrete molecules or bulk materials. These nanomaterials when conjugated with other ligands such as monoclonal antibodies, peptides or small molecules can be used to target tumor cells and microenvironment with incredibly high specificity and affinity. Nanoparticles inherently posses a large surface area. Making them ideal for attaching multiple ligands to to create a single nanoparticle that could be used for both tumor imaging and treatment.

There are several barriers that must be overcome before these new methods can be applied clinically:

Firstly the problem of nanoparticle surface opsonisation must be overcome. Nanoparticle surface opsonisation is the process of attaching proteins and other molecules to the surface of the nanoparticle. At present this process is not efficient enough  with surface ‘fouling’ occurring where nonspecific proteins are attaching to the nanoparticles in place of the desired proteins.

Secondly the problem of nanoparticle tissue retention, targeting and tumor penetration must be addressed. These are all processes that are central to manufacturing an effective diagnostic tool and treatment method using nanoparticles.

Finally and very importantly the issue of nonbiodegradable  nanomaterials containing toxic elements must be investigated. Without an idea of the effects that these particles may have on tissue it would be inconceivable to clinically trial these treatments.

New innovative techniques need to be developed to overcome these stumbling blocks on the road to creating a nanoparticle treatment for Cancer.

To read more about this topic get the free article: Futuremedicine

-CT

Nanopaprika.eu was started back in 2007 by a Hungarian Chemistry PhD student Andras Paszternak. The website provides a great deal of communication and networking tools. Since 2007 the Nanopaprika community has grown to 2000+ members.

This virtual  international nanoscience community (TINC) comes equipped with personal chat and scientific forums ranging from Microscopy to Nanomedicine. The site now connects nano scientists from all over the globe and is media partners with more than 30 nano conferences dealing with different topics in 2009 and 2010 alone.

Nanopaprika.eu is open to all as long as they have a passion for Nano! With over 2000 scientists from across the globe Nanopaprika boasts a wealth of knowledge that any Nano enthusiast can put to good use.

- CT

Understandingnano.com was started when Earl Boysen (co-author of Nanotechnology for Dummies) observed the need for a website with easy to understand explanations on a wide variety of nanotechnology applications. Understandingnano.com provides clear and concise information that is accessible to people who may not have expertise in Nanotechnology.

It is especially pleasing to see that Understandingnano.com has a whole section dedicated to explaining the basics of the many aspects of nanotechnologies application in medicine. Whilst providing useful resources to allow the reader to delve deeper into subjects that they are most interested in.

Understandingnano.com is not limited to providing information about nanotechnologies but also provides resources relating to nanotechnology such as where to find degrees in nanotechnology, jobs and even new articles!

Understandingnano.com is a partnership between Earl and his wife, Nancy. Earl brings an understanding of the technical issues based upon a masters in Engineering Physics and 20 years of experience in integrated circuit manufacturing. Nancy is the author of over 90 books on technology related topics. Her writing skills make Understandingnano.com easy to understand and enjoyable to read.

Understandingnano.com is not affiliated with any corporation, institution, or government body and therefore its information and articles don’t contain any organizational bias. – CT