Saturday, January 10, 2015

Nanoparticle Vaccines: Next-Generation Vaccine Platforms




In Vaccine, authors Liang Zhao, Arjun Seth, Nani Wibowo, Chun-Xia Zhoa, Neena Mitter, Chengzhong Yu and Anton P.J. Middelberg contend: 
Vaccine development is historically based on Louis Pasteur's “isolate, inactivate, inject” paradigm. As vaccine development moves increasingly to draw on modern concepts of rational design, the number of candidate vaccines is increasing  [1] and [2]. Most candidate vaccines represent “minimalist” compositions[3], which typically exhibit lower immunogenicity. Adjuvants and novel delivery systems that boost immunogenicity are increasingly needed as we move toward the era of modern vaccines.
Nanotechnology offers the opportunity to design nanoparticles varying in composition, size, shape, and surface properties, for application in the field of medicine [4] and [5]. Nanoparticles, because of their size similarity to cellular components, can enter living cells using the cellular endocytosis mechanism, in particular pinocytosis [6]. These cutting-edge innovations underpinned a market worth US $6.8 billion in 2006 [7] and predicted to reach US $160 billion by 2015 [8]. Source: "Nanoparticle Vaccines",Vaccine, Vol.32, Issue 3, 9 January 2014,http://www.sciencedirect.com/science/article/pii/S0264410X13016319

Anil Mahapatro and Dinesh K. Singh describe the advantages of nanaparticle drug delivery in their research paper entitled, " Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines," which appeared in the Journal of Nanobiotechnology, (Source: http://www.jnanobiotechnology.com/content/9/1/55 Mahapatro and Singh provide the following analysis "

Polymer-based nanoparticles are submicron-sized polymeric colloidal particles in which a therapeutic agent of interest can be embedded or encapsulated within their polymeric matrix or adsorbed or conjugated onto the surface [6]. These nanoparticles serve as an excellent vehicle for delivery of a number of biomolecules, drugs, genes and vaccines to the site of interest in-vivo. During the 1980's and 1990's several drug delivery systems were developed to improve the efficiency of drugs and minimize toxic side effects [7]. The early nanoparticles (NPs) and microparticles were mainly formulated from poly-alkyl-cyanoacrylate. The initial enthusiasm for the use of microparticles in medicine was later on dampened due to the size of the microparticles. There is a size limit for the particles to be able to cross the intestinal mucosal barrier of the gastrointestinal (GI) tract after the drug has been delivered orally. Most often, macroparticles could not cross mucosal barrier due to their bigger sizes resulting in failed delivery of drugs. Nanoparticles on the other hand have an advantage over microparticles due their nano-sizes. They are also better suited for intravenous (i.v.) delivery [8] compared to microparticles. Nanoparticles, however, had a different set of problems of their own. They had a very short circulating life span within the body after intravenous administration. The nanoparticles administered intravenously were rapidly cleared from the body by phagocytic cells. The therapeutic effect of drugs delivered via nanoparticles was thus minimized and could not be sustained. In recent years the problem of phagocytic removal of nanoparticles has been solved by surface modification of nanoparticles [7]. The surface modification protected nanoparticles from being phagocytosed and removed from the blood vascular system after intravenous injections. Now, a wide variety of biomolecules, vaccines and drugs can be delivered into the body using nanoparticulate carriers and a number of routes of delivery. NPs can be used to safely and reliably deliver hydrophilic drugs, hydrophobic drugs, proteins, vaccines, and other biological macromolecules in the body. They can be specifically designed for targeted drug delivery to the brain, arterial walls, lungs, tumor cells, liver, and spleen. They can also be designed for long-term systemic circulation within the body." Source: http://www.jnanobiotechnology.com/content/9/1/55)

If we consider applications for the current outbreak of Ebola across West Africa the advantages are quite dramatic. One of the forerunners of nanovaccine technology applications for Ebola is Novovax. According to Emily Mullin, "In rodents and monkeys, Novavax recombinant glycoprotein (GP) nanoparticle vaccine was highly effective, generating antibodies against the virus in the blood of animals challenged with the 2014 Guinea Ebola strain, which is responsible for the current Ebola epidemic in West Africa." (Source: http://www.fiercevaccines.com/story/ebola-update-novavax-testing-nanoparticle-jab-glaxo-gets-emas-advice/2014-10-30) 
Yet, nanotechnology applications for future vaccines is not the only application which could benefit the current outbreak of Ebola. Ceres, a biotech company has developed a nanoparticle technology 'Nanotrap' which provides biofluid sample processing capabilities for a wide array of diagnostic applications and sample handling needs. (Source: http://www.eurekalert.org/pub_releases/2014-12/gmu-nnt120214.php)

During the current outbreak of Ebola raging through parts of West Africa several Ebola Treatment Units and Centers (ETU's and ETC's) shifted their policy to reduce the use of IV's particularly in late stage cases. The advantages of nanoparticle delivery platforms, particularly in treating VHF's should not be underestimated.  "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." (Source; http://newsoffice.mit.edu/2013/nanoparticle-vaccine-offers-better-protection-0925).Dr. Darrell Irvine, an MIT professor of materials science and engineering and biological engineering and the leader of the research team at MIT notes: "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.
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." Source: http://newsoffice.mit.edu/2013/nanoparticle-vaccine-offers-better-protection-0925)
Pulmonary drug delivery with nanoparticle vaccines will be the drug delivery platform for for future Ebola and VHF outbreaks, in addition to its applications across a wide spectrum of infectious disease. 




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