Most of nanomaterials including the ability to generate

Mostof the vaccine adjuvants that are currently being used or that are under developmentare of Nano-range particulates.(5) Compared to traditionalmaterials, nanomaterials can protect the antigen from the surroundingbiological environment , they can increase the antigens half-life and minimizethe systemic toxicity.

They also promote the delivery of immunomodulatory andimmunostimulatory substances to antigen presenting cells, or trigger theactivation of antigen-specific T cells. Nanomaterialsare particulate materials that have a length scale in the range of 1 nm to 100nm in at least one dimension. (5) A broader definition increases therange up to 1 mm, based on their similar physicochemical properties tonanoscale particles. They have unique physicochemical properties that includessize, shape, surface chemistry, roughness and surface coatings. They are nowbeing used in the production of vaccines in the form of adjuvants as they areknown to generate and or enhance immunological responses originating frominteractions at the Nano-bio interface. (6, 7) One of the most importantadvantages of engineered Nano-materials is that it is possible to control theirproperties through engineered design. This allows for the selection of the mosteffective adjuvant formulations to be used in vitro and in vivo and beapproached in a systemic fashion. For example, studies have demonstrated thatby controlling the physicochemical properties of nanomaterials including theability to generate aspect ratio, dispersion state, size and surfacefunctionalization, it is possible to modulate the immune activation and furtherenhance immune responses to antigens.

(8, 9) Aluminum based adjuvants can be examples of engineeredNano-materials .Aluminum based adjuvants are the most widely used adjuvants inhuman vaccines in the world. These adjuvants have been used to make vaccinesfor more than 80 years and are generally considered stimulators of Th2immunity. (9, 11)Aluminum based adjuvants are made with aluminum combined with another materialdepending on the commercial sources. They can be composed of aluminum hydroxidewhich is called Alhydrogel, aluminum phosphate which is called Adju-Phos,aluminum potassium sulfate which is called an Alum, aluminum hydroxyphosphatesulfate which has been shorten to AHSA or a mixture of aluminum and magnesiumhydroxides which is called Imject Alum.(11-14).

The two types ofaluminum adjuvant that are mostly used in vaccine production is aluminumoxyhydroxide and aluminum hydroxyphosphate. Both of these type of aluminumadjuvant consist of nanoparticles that form loose, micrometer sized aggregatesat circumneutral ph. (10, 11) Thesecommercially available aluminum salts have different physicochemicalproperties.

(14) For example, aluminum hydroxides are needle-likeparticles that have a diameter of 2 nm, while aluminum phosphates areplate-like particles with a primary size of 50 nm. However, their names do notcorrectly describe their adjuvant structures. X-ray diffraction analysis andinfrared spectroscopy have identified aluminum hydroxide adjuvant ascrystalline aluminum oxyhydroxide (AlOOH) and aluminum phosphate is determinedas amorphous aluminum hydroxyphosphate (Al (OH) x (PO4) y).

(14) Theunderstanding of the key physicochemical properties that determine the Nano-biointeraction and the stimulation of immune responses are still not known,however many experiments have been taking place to help broaden our knowledgein this area. Anexample was a study by Li et al., they studied the size effects of aluminumsalts using ovalbumin and Bacillus anthraces protective antigen protein asmodel antigens. (15) Aluminum hydroxide nanoparticles with meandiameters of 112 nm and 9 µm were prepared. It was demonstrated that aluminumhydroxide nanoparticles of 112 nm exhibited more potent antigen-specificantibody response than those of the 9 µm micro-sized particles.

The strongeradjuvant activity of Nano-sized particles was corresponded with their abilityto more effectively facilitate the uptake of the antigens because of the ligandexchange as the OVA protein contains up to two phosphate groups and these couldstrongly bind to aluminum instead of a hydroxyl group and because the aluminumhydroxide nanoparticles have a larger surface area which means they containmore binding sites for protein adsorption and therefore have a higher proteinadsorption capacity. (15) Anotherstudy was done by Wang et al. and they studied the effects of surface coating.They prepared phospholipid bilayer-coated aluminum nanoparticles of 50 nm insize through chemisorption. They compared these nanoparticles adjuvant effectswith the adjuvant effects of naked particles. The coated adjuvant was morereadily taken up by antigen-presenting cells and could induce robustantigen-specific humoral e.

g. antibody production and cellular immunoresponsese.g. cytokine production with less local inflammation. (16)  

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