Nanoemulsion vaccines

A novel technique for vaccinating against a variety of infectious diseases – using an oil-based emulsion placed in the nose, rather than needles – has proved able to produce a strong immune response against smallpox and HIV in two new studies.

The results build on previous success in animal studies with a nasal nanoemulsion vaccine for influenza, reported by University of Michigan researchers in 2003.

Nanoemulsion vaccines developed at the Michigan Nanotechnology Institute for Medicine and the Biological Sciences at U-M are based on a mixture of soybean oil, alcohol, water and detergents emulsified into ultra-small particles smaller than 400 nanometers wide, or 1/200th the width of a human hair. These are combined with part or all of the disease-causing microbe to trigger the body’s immune response.

The surface tension of the nanoparticles disrupts membranes and destroys microbes but does not harm most human cells due to their location within body tissues. Nanoemulsion vaccines are highly effective at penetrating the mucous membranes in the nose and initiating strong and protective types of immune response, Baker says. U-M researchers are also exploring nasal nanoemulsion vaccines to protect against bioterrorism agents and hepatitis B.

The smallpox results, which appear in the February issue of Clinical Vaccine Immunology, could lead to an effective human vaccine against smallpox that is safer than the present live-vaccinia virus vaccine because it would use nanoemulsion-killed vaccinia virus, says Baker.

Anna U. Bielinska, Ph.D., a research assistant professor in internal medicine at the U-M Medical School, and others on Baker’s research team developed a killed-vaccinia virus nanoemulsion vaccine which they placed in the noses of mice to trigger an immune response. They found the vaccine produced both mucosal and antibody immunity, as well as Th1 cellular immunity, an important measure of protective immunity.

When the mice were exposed to live vaccinia virus to test the vaccine’s protective effect, all of them survived, while none of the unvaccinated control mice did. The researchers conclude that the nanoemulsion vaccinia vaccine offers protection equal to that of the existing vaccine, without the risk of using a live virus or the need for an inflammatory adjuvant such as alum hydroxide.

In antibody immunity, antibodies bind invading microbes as they circulate through the body. In cellular immunity, the immune system attacks invaders inside infected cells. There is growing interest in vaccines that induce mucosal immunity, in which the immune system stops and kills the invader in mucous membranes before it enters body systems.

A National Institutes of Health program, the Great Lakes Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases, funded the research. If the federal government conducts further studies and finds the nanoemulsion smallpox vaccine effective in people, it could be a safer way to protect citizens and health care workers in the event of a bioterrorism attack involving smallpox, Baker says.

That would allay concerns about the current vaccine’s safety which arose in 2002. On the eve of the Iraq War, the Bush administration proposed a voluntary program to vaccinate military personnel and 500,000 health care workers with the existing vaccine to prepare for the possible use of smallpox virus as a biological weapon.

Introduction to nanopharmaceuticals

Nanomedicine is the medical application of nanotechnology. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and nanovaccinology.

A definition from the Academy of Pharmaceutical Sciences of Great Britain.

Nanopharmaceuticals represent an emerging field where the nanoscale element may refer to either the size of the drug particle or to a therapeutic delivery system. These therapeutic systems may be defined as a complex system consisting of at least two components, one of which is the active ingredient. In this field the concept of nanoscale is the range from 1 to 1,000nm. The definition includes polymer therapeutics, which share many characteristics with macromolecular prodrugs such as antibody conjugates of drugs.

The European Science Foundation definition.

Nanopharmaceuticals can be developed either as drug delivery systems or biologically active drug products.

This sub-discipline is defined as the science and technology of nanometre size scale complex systems, consisting of at least two components, one of which being the active ingredient. In this field the concept of nanoscale was seen to range from 1 to 1000 nm.

Nanopharmaceuticals as a big part of what nanomedicine is today. From the Ruth Duncan presentation.

Various kinds of nanoscale particles used for nanopharmaceuticals

Nanoparticles is a microscopic particle with at least one dimension less than 100 nm.

Liposomes is a spherical vesicle composed of a bilayer membrane. In biology, this specifically refers to a membrane composed of a phospholipid and cholesterol bilayer

Antibody conjugates
A conjugate vaccine is created by covalently attaching a poor antigen to a carrier protein, thereby conferring the immunological attributes of the carrier on the attached antigen. This technique for the creation of an effective immunogen is most often applied to bacterial polysaccharides for the prevention of invasive bacterial disease.

polymer therapeutics

From the Ruth Duncan presentation

Buckyballs and Nanotubes

Nanoemulsions is a type of emulsion in which the sizes of the particles in the dispersed phase are defined as less than 1000 nanometers. A nanoemulsion of soybean oil to create drops of 400-600 nanometers in diameter will kill many pathogens such as bacteria and viruses.

Quantum Dots is a semiconductor nanostructure that confines the motion of conduction band electrons, valence band holes, or excitons (bound pairs of conduction band electrons and valence band holes) in all three spatial directions. The confinement can be due to electrostatic potentials (generated by external electrodes, doping, strain, impurities), the presence of an interface between different semiconductor materials (e.g. in core-shell nanocrystal systems), the presence of the semiconductor surface (e.g. semiconductor nanocrystal), or a combination of these

Small quantum dots, such as colloidal semiconductor nanocrystals, can be as small as 2 to 10 nanometers, corresponding to 10 to 50 atoms in diameter and a total of 100 to 100,000 atoms within the quantum dot volume. Self-assembled quantum dots are typically between 10 and 50 nm in size. Quantum dots defined by lithographically patterned gate electrodes, or by etching on two-dimensional electron gases in semiconductor heterostructures can have lateral dimensions exceeding 100 nm. At 10 nm in diameter, nearly 3 million quantum dots could be lined up end to end and fit within the width of a human thumb.

Dendrimers - Dendrimers are synthetic polymers, a thousand times smaller than cells. Dendrimers can be synthesized in various predetermined sizes, and can interact with biological agents by modifying their surface properties.

FURTHER READING
An article on nanopharmaceuticals and veterinary medicine

Presentation by Ruth Duncan on nanopharmaceuticals

A nanopharmaceuticals site