Pranchi Sharma Rajeswari Devanathan

Types of Vaccination
Passive Immunisation

Antitoxins and immunoglobulins which provide immediate source of antibody Ex: Diphtheria anti-toxin

Active Immunisation Live vaccines

attenuated (weakened)

Botulinum anti-toxin
Hep B IG, Tetanus IG

organism which replicates in the host Ex: MMR,varicella Killed/inactivated/subunit vaccines killed micro-organisms, inactivated toxins or other subunits Ex: Inactivated polio vaccine, DTaP vaccine

Nanovaccine
Nano is very vast field and it can be applied to any area, one of such

area is vaccine.
It provide a different routes of administration of vaccine. Nano vaccine can be designed, manufactured and introduced in to

the human body to improve health, including cellular repairs at the molecular level.
The nano material is so small that it can easily enter the cell;

therefore, nano materials can be used in-vivo or in-vitro for biological applications.

Nanolevel vaccine delivery

1. Nanobead: Inert solid bead
Size range 20-200nm. When antigens are adsorbed on the surface of bead it has been

shown to stimulate CD8-T cell response.

The size of the bead play a major role in eliciting a combined

response of humoral and cell-mediated immunity.

Antigen covalently linked to inert nano-beads with a size of ~50nm is preferentially taken up by DCs, thus inducing humoral as well as cellmediated immune responses

2. Polymeric nanoparticles
Biodegradable, biocompatible polymers have been approved for use

in humans. Poly (D,L-lactide-co-glycolide) (PLG) and polylactide (PLA).

Antigen

Absorbed

Entraped

Contd..
PLG have been extensively used to encapsulate antigens. PLG forms lactic and glycolic acids, After hydrolysis of hydroxyl

acids, yielding small spherical polymeric particles 1100 nm in size.

Adsorbed antigen offer improved stability and activity over

encapsulated antigen by avoiding exposure to organic solvents used during formulation and acidic pH conditions caused by degradation of the polymer.

3. Nanoemulsion
Size of globule (100-400nm) Nano-emulsion vaccine does not require refrigeration and is stable

for 6 months.
Nano-emulsion is non-toxic, pain free and avoids the risk of

spreading needle-borne infections.

Nano-emulsion of hepatitis B antigen, has been reported to be a safe

and effective hepatitis B vaccine.

4. Viral

vectored vaccines

Viruses size vary in diameter from 20 nanometers (nm;

0.0000008inch) to 250400nm.
The immune system quickly respond to viruses, this would seem to

be an ideal way to deliver an antigen.

It consist of a non-replicating virus that contains some defined

genetic material from the pathogen to which immunity is desired. Such vaccines are also commonly referred to as live recombinant vaccines.

Advantages of virallyvectored vaccines include their ease of production, a good safety profile, ability to potentiate strong immune responses, potential for nasal or epicutaneous delivery and mucosal immunization.

Advantages

Disadvantages

Nanovaccine have potential to deliver safe and more effective vaccine. Nanobead covalently coupled with antigen offer distinct advantagesa low dose of antigen is required, efficient processing by antigen-presenting cells and stability during storage. Encapsulated nanoparticles easily deliver antigen, protects the antigen from degradation and is found to be effective with a single dose due to slow release of the antigen. Many of the nanovaccines are non-invasive, delivered by the oral or nasal route, diffusion patches or micro needle arrays, thus allowing pain-free delivery with minimal damage.

Cost of production. Small nanoparticles are cleared quickly from the body, large counter parts may accumulate in vital organs causing toxic problems. Reproducibility of formulation during manufacturing is one of the major hurdles in the use of nanoparticles as vaccines.

Did You Know?

A young person with Type 1 diabetes will use up to 1500 syringes a year - Associate Professor John Fitzgerald, School of Population Health, University of Melbourne, July 2007 Globally, around 30 billion syringes are used per year; 800 million are used by Australians.

WHAT NOW ?
9 October 2012 Vaxxas, a biotechnology company commercializing a novel vaccine delivery platform, has initiated a research collaboration with Merck, known as MSD outside the US and Canada. Vaxxas has granted Merck an exclusive license for the Nanopatch platform for commercial production of an undisclosed vaccine candidate

What if you never had to have another needle? Nanopatch array

Penetrates through the

protective outer skin layer (stratum corneum) and targets immune-activating material to the immune-cell rich layers just beneath the outermost skin layer utilising the microprojections with optimised spacing and length
A square patch is kept on the

skin for two minutes to direct the vaccine. This technique uses 100th part of the dose of a needle and shows equivalent or better performance.

Preclinical study in mouse model

Either reducing the dose

required to achieve efficacy (100-fold reduction has been achieved in the mouse model when delivering Fluvax), and for amplifying the vaccine efficacy

Pre-clinical experiments have also shown the ability of the Nanopatch to remove or significantly reduce the amount of adjuvant required for effective vaccination.

Protrusions can be specifically engineered to ensure:

Delivery directly to immune cells

therefore less material required

Painless application and no scar tissue

formation
Versatility in applications: vaccines,

drugs, hormones, wound healing proteins.

Advantages of Nanopatch
Delivery of nano-sized particles directly to the immune system

Delivery of molecules that normally cannot penetrate the skin

Lower dosages = less side effects Easy to use, no needle-stick injury, low risk of infection, pain-free Can be self-administered, or given by a non-medical person Smaller, lighter, lower transport cost Mass production = cost benefits Suitable for public health programs e.g. air-drop into disaster zones

Suitable for veterinary purposes

Biocompatible and biodegradable material used to make patches Can achieve short- & long-term delivery

Patent
First patent was issued in Jan. 2012.

There are around 11 applications pending; in the US, Canada, Europe and other first tier economies, and select emerging markets, or > 90% of the worldwide market for pharmaceuticals. The company continues to file new applications, approximately quarterly.

Navacim

Navacim was first manufactured by Parvus Therapeutics Inc. Calgary Navacim is a new class of therapeutic; a peptide-MHC complex covalently linked to a nanoparticle

Nanoparticle core gold/iron B. Surface coating agent Protein component C. MHC protein, D. Short Anitgenic peptide for specific disease. 10-20 amino acids long E. Finished particle size 60nm
A.

Disease condition
Pancreatic cells

Antigen from damaged cells

APC

Memory T cells CTL

Mode of action
A

. CTLs are normally programmed to die when they re-encounter antigen on their target cell so, not surprisingly, they also die if they recognize and interact with the p-MHC on the Navacim B . The autoregulatory memory T cells don't need co-stimulation so the Navacim expands them and they go on to target and remove the diseaseassociated APCs all of them

More T memory cells

Navocim

Destruction of T cytotoxic cells

Future prospects
Carbon nanotubes may be used to deliver vaccine. Peptidenano-bead based vaccine approach may be beneficial,

especially for highly variable pathogens such as FMDV(foot and mouth disease virus). Nano emulsion may deliver smallpox, influenza, anthrax and HIV vaccines. Nanoemulsion against GP120, one of the major binding proteins, may induce mucosal and cellular immunity, and neutralize antibody to various isolates of HIV. Adenovirus may deliver vaccine for Alzheimer's disease, influenza, tetanus and HIV based vaccine.

References
Tarala Dnandedkar, Nanovaccines: recent developments in

vaccination, J.Biosci.340000002009.
J.Peek Lauraet.al, Nanotechnology in vaccine delivery, Advanced

Drug Delivery Reviews60(2008)915928

J.Bharali Dhrubaet.al, Novel nanoparticles for the delivery of

recombinant hepatitis B vaccine, Nanomedicine: Nanotechnology, Biology, and Medicine4(2008)311317

Cui Zhengrong et.al, The effect of co-administration of adjuvants with

a nanoparticle-based genetic vaccine delivery system on the resulting immune responses, European Journal of Pharmaceutics and Biopharmaceutics 55 (2003).