Intraperitoneal Administration of Calcium Phosphate Nanoparticles Encapsulating pSVβgal Elicits Immune Response to Encoded Protein

Bacille Calmette-Guerin (BCG) still the only authenticated vaccine against tuberculosis. Due to its drawbacks, a need for a new formula has emerged. The implication of “Nanovaccinology” is one of the possible alternatives. The non-viral vectors have a low transfection ability. In the context, this work aims to add two adjuvants to a calcium phosphate nanoparticles (CPNPs) functionalized with early secreted antigenic target 6-kilo dalton ( ESAT-6) cloned pcDNA3.1(+) plasmid. ESAT-6 gene is specific to mycobacterium tuberculosis complex (MTC) and encodes a T-cell antigen. The adjuvants in practice are Herring protamine and cytosine-phosphodiester bond-guanosine-oligodeoxynucleotide 7909 ( CpG-ODN 7909). Each has a different strategy in enhancing immune response; protamine is particulate adjuvant while CpG is an immunopotentiator substance. Nano complex was transfected into THP-1 monocytic cell line after its activation to a macrophage via 100nM PMA. Cellular immune response, interleukin-12 (IL-12), and tumor necrosis factor –alfa (TNF-ɑ) also ESAT-6 protein production were assayed via the Sandwich ELISA technique. Results revealed that CPNPs offer only partial protection to the adsorbed plasmid against enzymatic degradation. Nano complex formula with two adjuvants resulted in significantly higher cellular immune response comparing to formula carrying one adjuvant. In conclusion, the implication of CPNPs in gene delivery accompanied with two adjuvants each possess different strategy, will result in partial protection to the delivered gene with upsurge cellular immune response.

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Calcium phosphate nanoparticles show an effective activation of the innate immune response in vitro and in vivo after functionalization with flagellin

Virologica Sinica ◽

10.1007/s12250-014-3379-0 ◽

2013 ◽

Vol 29 (1) ◽

pp. 33-39 ◽

Cited By ~ 17

Author(s):

Diana Kozlova ◽

Viktoriya Sokolova ◽

Maohua Zhong ◽

Ejuan Zhang ◽

Jingyi Yang ◽

...

Keyword(s):

Immune Response ◽

Calcium Phosphate ◽

Innate Immune Response ◽

Innate Immune ◽

Effective Activation ◽

Calcium Phosphate Nanoparticles ◽

Immune Response In Vitro

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The Potential of Calcium Phosphate Nanoparticles as Adjuvants and Vaccine Delivery Vehicles

Frontiers in Materials ◽

10.3389/fmats.2021.788373 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhe Sun ◽

Wenyi Li ◽

Jason C. Lenzo ◽

James A. Holden ◽

Michael J. McCullough ◽

...

Keyword(s):

Immune Response ◽

Calcium Phosphate ◽

Vaccine Development ◽

Vaccine Delivery ◽

Vaccine Design ◽

Cost Effective ◽

Research Groups ◽

Immunological Effects ◽

Calcium Phosphate Nanoparticles ◽

Delivery Vehicles

Vaccination is one of the most efficacious and cost-effective ways to protect people from infectious diseases and potentially cancer. The shift in vaccine design from disrupted whole pathogens to subunit antigens has brought attention on to vaccine delivery materials. For the last two decades, nanotechnology-based vaccines have attracted considerable attention as delivery vehicles and adjuvants to enhance immunogenicity, exemplified with the current COVID vaccines. The nanoparticle vaccines display unique features in protecting antigens from degradation, controlled antigen release and longer persisting immune response. Due to their size, shape and surface charge, they can be outstanding adjuvants to achieve various immunological effects. With the safety and biodegradable benefit of calcium phosphate nanoparticles (CaP NPs), they are an efficient carrier for vaccine design and adjuvants. Several research groups have studied CaP NPs in the field of vaccination with great advances. Although there are several reports on the overview of CaP NPs, they are limited to the application in biomedicine, drug delivery, bone regeneration and the methodologies of CaP NPs synthesis. Hence, we summarised the basic properties of CaP NPs and the recent vaccine development of CaP NPs in this review.

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Enhancing Immune Responses to a DNA Vaccine Encoding Toxoplasma gondii GRA7 Using Calcium Phosphate Nanoparticles as an Adjuvant

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.787635 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hong-Chao Sun ◽

Jing Huang ◽

Yuan Fu ◽

Li-Li Hao ◽

Xin Liu ◽

...

Keyword(s):

Immune Response ◽

Calcium Phosphate ◽

Toxoplasma Gondii ◽

Parasite Burden ◽

Vaccination Strategy ◽

Dense Granule ◽

Antigen Delivery ◽

Humoral Immune ◽

Calcium Phosphate Nanoparticles ◽

Almost All

Toxoplasma gondii infects almost all warm-blooded animals, including humans. DNA vaccines are an effective strategy against T. gondii infection, but these vaccines have often been poorly immunogenic due to the poor distribution of plasmids or degradation by lysosomes. It is necessary to evaluate the antigen delivery system for optimal vaccination strategy. Nanoparticles (NPs) have been shown to modulate and enhance the cellular humoral immune response. Here, we studied the immunological properties of calcium phosphate nanoparticles (CaPNs) as nanoadjuvants to enhance the protective effect of T. gondii dense granule protein (GRA7). BALB/c mice were injected three times and then challenged with T. gondii RH strain tachyzoites. Mice vaccinated with GRA7-pEGFP-C2+nano-adjuvant (CaPNs) showed a strong cellular immune response, as monitored by elevated levels of anti-T. gondii-specific immunoglobulin G (IgG), a higher IgG2a-to-IgG1 ratio, elevated interleukin (IL)-12 and interferon (IFN)-γ production, and low IL-4 levels. We found that a significantly higher level of splenocyte proliferation was induced by GRA7-pEGFP-C2+nano-adjuvant (CaPNs) immunization, and a significantly prolonged survival time and decreased parasite burden were observed in vaccine-immunized mice. These data indicated that CaPN-based immunization with T. gondii GRA7 is a promising approach to improve vaccination.

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One-pot synthesis of injectable methylcellulose hydrogel containing calcium phosphate nanoparticles

Carbohydrate Polymers ◽

10.1016/j.carbpol.2016.10.055 ◽

2017 ◽

Vol 157 ◽

pp. 775-783 ◽

Cited By ~ 22

Author(s):

Hanna Park ◽

Min Hee Kim ◽

Young Il Yoon ◽

Won Ho Park

Keyword(s):

Calcium Phosphate ◽

One Pot ◽

One Pot Synthesis ◽

Calcium Phosphate Nanoparticles

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Calcium phosphate phase transition in the presence of Aminosilane

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s205327331409932x ◽

2014 ◽

Vol 70 (a1) ◽

pp. C67-C67

Author(s):

Babak Mostaghaci ◽

Brigitta Loretz ◽

Robert Haberkorn ◽

Guido Kickelbick ◽

Claus-Michael Lehr

Keyword(s):

Phase Transition ◽

Calcium Phosphate ◽

Blood Compatibility ◽

Transfection Efficiency ◽

Hek293 Cells ◽

Step Method ◽

Calcium Phosphate Nanoparticles ◽

Amine Groups ◽

The Impact

Calcium phosphate has been the point of interest for in vitro gene delivery for many years because of its biocompatibility and straight forward application. However, there are some limitations regarding in vivo administration of these particles mostly because of vast agglomeration of the particles and lack of strong bond between the particles and pDNA. We introduced a simple single step method to functionalize calcium phosphate nanoparticles with Aminosilanes having a different number of amine groups. The nanoparticles were characterized chemically and structurally and their toxicity and interaction with pDNA were studied as well. Results revealed that different crystalline phase of calcium phosphate nanoparticles (Brushite and Hydroxyapatite) with a size below 150 nm were prepared, depending on conditions of synthesis and phase, each with a narrow size distribution. The aminosilane agents caused oriented nucleation and growth of crystallites and can decrease the pH for producing hydroxyapatite phase. The phenomenon could be revealed with the presence of anisotropy in the structure of synthesized hydroxyapatite. The number of amine groups in the Aminosilane agent could change the phase transition pH. Brushite particles revealed to have stronger interaction with pDNA mostly because of their higher positive surface charge. Both particles showed blood compatibility and negligible toxicity. Transfection experiment revealed the capability of both brushite and hydroxyapatite particles to transfect A549 and HEK293 cells. The new modified nanoparticles can be stored in a dried state and re-dispersed easily at the time of administration. Moreover, the transfection efficiency is higher in comparison with conventional calcium phosphate. This study showed the impact of presence and type of the modifying agent on the crystal structure and the amount of surface functionalization of nanoparticles, which in consequence influenced their interaction with cells.

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