Nasal anthrax vaccine research at U of Michigan

Some interesting research done in Dr. James R. Baker Jr.’s lab at University of Michigan was reported this week. Baker is the Director of the University’s Nanotechnology Institute for Medicine and Biological Sciences.

Baker, an immunologist, developed a nontoxic nanoemulsion made of soybean oil droplets that carry antigens into the nasal mucosa where they stimulate an immune response. (See description of the vaccine project here.) His nanoemulsion research was funded by DARPA’s Unconventional Pathogen Countermeasures Program, while the vaccine development was funded by the NIH.

As Baker’s research projects page explains, there are some serious drawbacks to the current vaccines we have for both anthrax and smallpox, and a completely harmless soybean oil carrier could solve a lot of problems.

As current approaches to vaccination for agents such as small pox and anthrax have drawbacks due to the use of live virus, complex vaccination protocols or the addition of unacceptable adjuvants (for humans), we are currently determining whether mixing nanoemulsion with vaccinia will provide a rapid and effective means for a killed vaccinia virus vaccine. We will initially test the ability of the nanoemulsion to inactivate vaccinia virus. We will then evaluate the immunogenicity of vaccinia virus mixed with nanoemulsion and placed either in the nares or injected intradermal or intramuscularly. After the immune responses have been characterized, we will then determine if mice immunized with vaccinia/nanoemulsion are protected from infection with live vaccinia virus. These studies should determine the feasibility of a nanoemulsion-based killed vaccinia virus vaccine, and provide a basis for subsequent efficacy studies using primate models of small pox.

We plan to study the efficacy of nanoemulsion mixed with protective antigen of B. anthracis (PA) for the development of protective immunity against inhalation or injection challenge with either live bacilli or spores. Similar studies on the efficacy of nanoemulsion mixed with HIV and other agents are in progress.

I’ve not had the anthrax shots, luckily, but friends tell me it’s a royal pain and there are all those boosters. It could be that a series might be needed with the nasal vaccine, too, but it would be a more pleasant experience, I’m sure. Animal studies indicated that for inhalational anthrax, the nasal vaccine was partially effective but it did extend survival time. From New Scientist:

An exposure of 10 times the lethal dose killed 30% of the guinea pigs, and 100 times the lethal dose killed 60%. This is about the same level of effectiveness as that offered by conventional anthrax vaccines, which were developed 30 years ago.

The vaccine also extended survival time by between three and five days, which in humans might allow enough time for other treatments to work.

Extending survival time is very important now that a treatment’s been developed—remember ABThrax, which I blogged about here.

Baker’s lab is also working on research with dendrimers for targeted delivery of whatever-you-want, a project I find quite a bit more intriguing in all sorts of ways than the nasal vaccine.

Incidentally, I heard Baker speak on biosecurity a couple of years ago. He discussed a variety of examples of research that highlighted the range of potential future biothreats. He emphasized the need to educate health care professionals and that traditional bioagents found in nature might be missed by doctors because they cause different symptoms when delivered as a weapon. He was supportive of developing biosecurity measures that have dual uses, in other words are good public health measures whether someone attacks us or not.

And that seems to be the direction we are attempting to stumble in.

The length factor in nanotube uptake

Just a quick but interesting blurb here.

NIST experiments using human lung cells demonstrate that DNA-wrapped single-walled carbon nanotubes longer than about 200 nanometers are excluded from cells, while shorter lengths are able to penetrate the cell interior. Abstract

Not only is this important to help develop our understanding of possible toxic effects of nano-materials, it also adds to research in drug or gene therapy delivery.

 

h/t Biosingularity.

Toward universal biosensors

Here are a couple of interesting news items to share on the topic of micro- to nanoscale sensors that can be designed to indicate multiple substances in solution whether the target is DNA, protein, other biomolecules, or pollutants.

First, Science has a paper titled Multifunctional Encoded Particles for High-Throughput Biomolecule Analysis, which describes the use of microfluidics in the construction of “barcoded” (I use that loosely) biosensor particles that could be built to sense multiple compounds (they were tested with DNA). The particles are made of a polyethylene glycol (PEG) and measure 90 µm in width, ~30 µm in thickness, and 180 to 270 µm in length. (For reference, a red blood cell is about 6-8 µm in diameter and eukaryotic cells range from about 2-100 µm.)

Construction of the particles:

Fig. 1. (A) Schematic diagram of dot-coded particle synthesis showing polymerization across two adjacent laminar streams to make single-probe, half-fluorescent particles [shown in (B)]. (C) Diagrammatic representation of particle features for encoding and analyte detection. Encoding scheme shown allows the generation of 220 (1,048,576) unique codes. (D) Differential interference contrast (DIC) image of particles generated by using the scheme shown in (A). (E to G) Overlap of fluorescence and DIC images of single-probe (E), multiprobe (F, bottom), and probe-gradient (G, left) encoded particles. Shown also is a schematic representation of multiprobe particles (F, top) and a plot of fluorescent intensity along the center line of a gradient particle (G, right). Scale bars indicate 100 µm in (D), (F), and (G) and 50 µmin(E).

Oligonucleotide probe-coated particles demonstrated multiplexing capability by indicating multiple targets with high specificity after 10 minutes. In addition, the researchers constructed a flow-through reader for the particles, demonstrating the full system from start to finish. These particles could be constructed with multiple segments that detect a variety of different types of compounds all on one particle. This technology has huge potential. Abstract or Full (subscription)

Next up, another technology that has been in development for a couple of years, barcoded biosensing nanowires developed by LLNL’s BioSecurity and Nanosciences Laboratory. LLNL came up with a way of constructing nanoscale wires with gold, silver, and nickel stripes, essentially barcodes.

The nanowires carry fluorescent-tagged antibodies specific to biowarfare agents. Each type of antibody is attached to wires with a certain barcode. The nanowires will be used in solution for rapid, single and multiplex immunoassays.

If you have access to Angewandte Chemie, the paper is here. If not, there’s more here.

Finally, not really a “universal biosensor” but interesting in any case: Georgia Institute of Technology researchers have come up with a way to convert the silica shells of diatoms into silicon replicas. The silicon structures retain the original diatom shapes, which are suitable for nanoscale gas sensors. Part of the abstract from the Nature article:

…nanostructured silica microshells (frustules) of diatoms (unicellular algae) were converted into co-continuous, nanocrystalline mixtures of silicon and magnesia by reaction with magnesium gas. Selective magnesia dissolution then yielded an interconnected network of silicon nanocrystals that retained the starting three-dimensional frustule morphology. The silicon replicas possessed a high specific surface area (>500 m2 g-1), and contained a significant population of micropores (less than or equal to20 Å). The silicon replicas were photoluminescent, and exhibited rapid changes in impedance upon exposure to gaseous nitric oxide (suggesting a possible application in microscale gas sensing). This process enables the syntheses of microporous nanocrystalline silicon micro-assemblies with multifarious three-dimensional shapes inherited from biological or synthetic silica templates for sensor, electronic, optical or biomedical applications.

a, Secondary electron image of an electroded microporous silicon frustule replica. b, Electrical response of this single silicon frustule sensor to NO(g). DeltaZ is the impedance change upon exposure to NO(g), and Zo is the sensor impedance in pure flowing argon.

More here at GA Tech.

5 minutes to midnight: doomsday clock

Those party-pooping atomic scientists have decided it’s time for an even more grim outlook on the future of mankind. We’re now two minutes closer to midnight.

Under the category of emerging technologies the rationale for a two-minute advance includes the life sciences, which has spawned technologies at an ever-accelerating pace since the 1970s—hurtling us toward a very uncertain future that could heal us all, or kill us all.

Unlike the biological weapons of the last century, these new tools could create a limitless variety of threats, from new types of “nonlethal” agents, to viruses that sterilize their hosts, to others that incapacitate whole systems within an organism. The wide availability of bioengineering knowledge and tools, along with the ease with which individuals can obtain specific fragments of genetic material (some can be ordered through the mail or over the internet), could allow these capabilities to find their way into unspecified hands or even those of backyard hobbyists. Such potential dangers are forcing scientists, institutions, and industry to develop self-governing mechanisms to prevent misuse. But developing a system to ensure the safe use of bioengineering, without impeding beneficial research and development, could pose the greatest international science and security challenge during the next 50 years.

Further, there’s the dark promise of nanotechnology:

Nanotechnology’s interaction with other sciences, particularly the life sciences, raises the potential of integrating nanoparticles into biological agents that might cause harm to humans and other species. Some experts express concern that nanotechnology could be integrated into miniature, invasive surveillance systems or could prompt a molecular arms race with small but powerful weapons. The potential military applications of nanotechnology are vast, from lighter, stronger materials for weapons, sensors, and electronics, to futuristic interfaces between machines and human functioning.

A few nanotechnology notes

First off, I noticed this tidbit this morning, Researchers use laser, nanotechnology to rapidly detect viruses. Scientists at University of Georgia say they have come up with a nanomaterial-based “amplifier” that will make even a single virion in solution detectable by surface-enhanced Raman spectroscopy (SERS). They are currently working to build a library of spectra for various viruses. Using nanoparticles for SERS has been reported in the past; what is new here, apparently, is the way the particles are arranged on the surface to amplify the signal.

Raman spec has been used as a rapid method for chemical agent detection and hand held or mobile units are available commercially for use by first responders and the like. Here’s one I’ve seen demonstrated. BUT…the problem with using this method for biodetection is you still have to get a sample of probably a body fluid to test, and of course this requires the cooperation of individuals who, for example, might be passing through an airport.

For some background, here’s a nice, short article covering some current research in detection methods; unfortunately, they didn’t post a date but it contains references from 2006.

Next on this morning’s reading list, Nature published an article this week proposing “five grand challenges” to research that will enable us to get a better handle on the risks of nanotechnology. Boiled down, here’s the list and a couple of excerpts:

Develop instruments to assess exposure to engineered nanomaterials in air and water, within the next 3–10 years.

Three issues stand out as fertile ground for innovative research: monitors for airborne exposure, detectors for waterborne nanomaterials, and smart sensors that can measure both exposure and potential hazards.

Develop and validate methods to evaluate the toxicity of engineered nanomaterials, within the next 5–15 years.

…there are three that we consider crucial for stimulating high-quality research and preventing the unnecessary use of hazardous nanomaterials: validated screening tests, developing viable alternatives to in vivo tests, and determining the toxicity of fibre-shaped nanoparticles.

Develop models for predicting the potential impact of engineered nanomaterials on the environment and human health, within the next 10 years.

…develop validated models capable of predicting the release, transport, transformation, accumulation and uptake of engineered nanomaterials in the environment. In parallel, validated models must be developed that are capable of predicting the behaviour of engineered nanomaterials in the body, including dose, transport, clearance, accumulation, transformation and response.

Develop robust systems for evaluating the health and environmental impact of engineered nanomaterials over their entire life, within the next 5 years.

Develop strategic programmes that enable relevant risk-focused research, within the next 12 months.

Finally, hey, I’m a bugs ‘n’ gas gal. What do I care about nanotech anyway? Well, improving detection technologies as discussed above is naturally of interest. But for an interesting perspective on other military implications of nanotech, see this NATO committee report from last year and check out Section III. Military Uses of Nanotechnology, Section IV. Implications on Military Strategies and the Balance of Power, and Section V. Implications on International Non-Proliferation and Arms Control Regimes.