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Momtezuma Tuatara
19-03-09, 07:31 AM
http://www.sciencedaily.com/releases/2009/03/090317162846.htm (http://www.sciencedaily.com/releases/2009/03/090317162846.htm)


Goodbye Needle, Hello Smoothie: New Generation Oral Vaccine Uses Dairy Probiotics To Protect Against Disease

ScienceDaily (Mar. 18, 2009) ­ Instead of a dreaded injection with a needle, someday getting vaccinated against disease may be as pleasant as drinking a yogurt smoothie.

A researcher from the Northwestern University Feinberg School of Medicine has developed a new oral vaccine using probiotics, the healthy bacteria that are found in dairy products like yogurt and cheese. He has successfully used the approach in a preclinical study to create immunity to anthrax exposure. He also is using the method to develop a breast cancer vaccine and vaccines for various infectious diseases.

This new generation vaccine has big benefits beyond eliminating the "Ouch!" factor. Delivering the vaccine to the gut -- rather than injecting it into a muscle -- harnesses the full power of the body's primary immune force, which is located in the small intestine.

"This is potentially a great advance in the way we give vaccines to people," said Mansour Mohamadzadeh, the lead author and an associate professor of medicine in gastroenterology at the Feinberg School.

"You swallow the vaccine, and the bacteria colonize your intestine and start to produce the vaccine in your gut," Mohamadzadeh said. "Then it's quickly dispatched throughout your body. If you can activate the immune system in your gut, you get a much more powerful immune response than by injecting it. The pathogenic bacteria will be eliminated faster."

Most vaccines consist of protein and won't maintain their effectiveness after being digested by the stomach. However, the lactobacillus protects the vaccine until it is in the small intestine.

The Northwestern study was reported in a recent issue of the Proceedings of the National Academy of Science.

There are other advantages to the new oral vaccine. Probiotics, which are natural immune stimulators, eliminate the need for a chemical in traditional vaccines that inflames the immune system and triggers a local immune response. The chemical, called an adjuant, may cause side effects such as dizziness, arm swelling and vomiting. Probiotic vaccines also are inexpensive to produce.

The specially engineered vaccine gives more immune bang for the buck than an injected one because it induces a local and a systemic immune response.

The vaccine targets the first line of gut immune cells called dendritic cells -- the commanders-in-chiefs of the immune system. They engulf the vaccine then instruct the immune system's foot soldiers -- killer T-cells and B-cells -- to seek out and destroy any cells in the body infected with a particular bacterium or virus.

In the study, Mohamadzadeh fed mice the new oral anthrax vaccine, and then exposed them to anthrax bacteria. Eighty percent of the mice survived, which is comparable to the results when mice were injected with anthrax vaccine, he said.

"Their immune response was higher and more robust than with the injected vaccine," Mohamadzadeh said. The mice generated a much higher T and B immunity against the pathogenic bacteria.

Mohamadzadeh's vaccine technology can be applied to many other diseases. He is developing an oral vaccine for breast cancer using probiotics. The vaccine would use the Her2/neu breast cancer antigen, a protein highly produced by breast tumor cells, and train the immune system to destroy any cells producing Her2/neu, he said.

In addition, Mohamadzadeh has developed a "multi-tasking" cancer vaccine against breast, colon and pancreatic cancer that soon will be tested in mouse models.

The technology also can be used to develop a probiotic vaccine for HIV, hepatitis C and the flu, he said.

Terrence Barrrett, M.D., chief and professor of gastroenterology at the Feinberg School, said delivering a vaccine to the gut is the most logical route.

"Nature isn't used to seeing antigens injected into a muscle," said Barrett, who also is a physician at Northwestern Memorial Hospital. "The place where your immune system is designed to encounter and mount a defense against antigens is your gut."

The study was funded by the National Institutes of Health and the North Carolina Dairy Foundation.


Journal reference:
M. Mohamadzadeh, T. Duong, S. J. Sandwick, T. Hoover, and T. R. Klaenhammer. Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge. Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0900029106 (http://dx.doi.org/10.1073/pnas.0900029106)

unherdof
19-03-09, 09:28 AM
I got a major ick factor reading this... still processing it actually.

Serephina
19-03-09, 11:27 AM
It will be very interesting to see how this develops. I wonder how adverse reactions compare with the injectable vaccines.

The only thing that concerns me is the possibility of governments being sneaky add adding this stuff to supermarket yogurts and other foods.

MinorityView
19-03-09, 12:23 PM
I don't think they would do that, because how would they make the billions of bucks if they were including it in the cost of a carton of yogurt?

unherdof
19-03-09, 12:49 PM
The dairy lobby is positively huge in the US. As is grain, sugar and corn... none of which humans have evolved to eat. Anytime I see that stupid food pyramid I see red, and this is beside the fact that it was created by the grain industry (hence the exorbitant amount of grain servings recommended daily). Ugh.

Momtezuma Tuatara
19-03-09, 02:13 PM
What would happen though, if, when the dendritic cells "engulf the vaccine" which is something inside the lacto, the lacto part of this vaccine is included in it's immune response? What say the lacto becomes an antigen, and is then wiped out through the body?

Are mice, bumans?

Momtezuma Tuatara
20-03-09, 05:11 PM
To better understand mucosal vaccines read this:

http://www.brown.edu/Courses/Bio_160/handouts/feb23.pdf

magical1
20-03-09, 05:24 PM
Putting up my hand and saying that goes right over my head! :confused: :o

Momtezuma Tuatara
20-03-09, 05:27 PM
Please try again, magical 1. You might understand it, if you go through it a few times.... This is the next step for pharmaceutical, and you need to understand the previous one, to get why this one has both promise, and... potential disaster:

nano emulsion based vaccines (http://www.nanobio.com/News/documents/Vaccineconference8_08.pdf). This is the future, so please try to understand it.

Momtezuma Tuatara
20-03-09, 05:30 PM
They've alread started this process:

http://iai.asm.org/cgi/content/full/75/8/4020?view=long&pmid=17502384

Here's the patent for a nano anthrax vaccine 1 Jan 2008 = http://www.freepatentsonline.com/7314624.html

And here's an evaluation of a new nano Hep B vaccine = http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002954

Momtezuma Tuatara
20-03-09, 05:33 PM
http://www.azonano.com/news.asp?newsID=8354

Momtezuma Tuatara
20-03-09, 05:37 PM
This is a very interesting abstract:

http://www.ncbi.nlm.nih.gov/pubmed/19168734?

Infect Immun. (http://javascript<b></b>:AL_get(this, 'jour', 'Infect Immun.');) 2009 Apr;77(4):1649-63. Epub 2009 Jan 21. Links (http://javascript<b></b>:PopUpMenu2_Set(Menu19168734);)

Killed but metabolically active Bacillus anthracis vaccines induce broad and protective immunity against anthrax.

Skoble J (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Skoble%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Beaber JW (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Beaber%20JW%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Gao Y (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Gao%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Lovchik JA (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lovchik%20JA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Sower LE (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Sower%20LE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Liu W (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Liu%20W%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Luckett W (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Luckett%20W%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Peterson JW (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Peterson%20JW%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Calendar R (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Calendar%20R%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Portnoy DA (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Portnoy%20DA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Lyons CR (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lyons%20CR%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Dubensky TW Jr (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Dubensky%20TW%20Jr%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Anza Therapeutics Incorporated, Concord, California 94520, USA. jskoble@yahoo.com
Bacillus anthracis is the causative agent of anthrax. We have developed a novel whole-bacterial-cell anthrax vaccine utilizing B. anthracis that is killed but metabolically active (KBMA). Vaccine strains that are asporogenic and nucleotide excision repair deficient were engineered by deleting the spoIIE and uvrAB genes, rendering B. anthracis extremely sensitive to photochemical inactivation with S-59 psoralen and UV light. We also introduced point mutations into the lef and cya genes, which allowed inactive but immunogenic toxins to be produced. Photochemically inactivated vaccine strains maintained a high degree of metabolic activity and secreted protective antigen (PA), lethal factor, and edema factor. KBMA B. anthracis vaccines were avirulent in mice and induced less injection site inflammation than recombinant PA adsorbed to aluminum hydroxide gel. KBMA B. anthracis-vaccinated animals produced antibodies against numerous anthrax antigens, including high levels of anti-PA and toxin-neutralizing antibodies. Vaccination with KBMA B. anthracis fully protected mice against challenge with lethal doses of toxinogenic unencapsulated Sterne 7702 spores and rabbits against challenge with lethal pneumonic doses of fully virulent Ames strain spores. Guinea pigs vaccinated with KBMA B. anthracis were partially protected against lethal Ames spore challenge, which was comparable to vaccination with the licensed vaccine anthrax vaccine adsorbed. These data demonstrate that KBMA anthrax vaccines are well tolerated and elicit potent protective immune responses. The use of KBMA vaccines may be broadly applicable to bacterial pathogens, especially those for which the correlates of protective immunity are unknown.
PMID: 19168734 [PubMed - in process]

Related Articles


The role of antibodies to Bacillus anthracis and anthrax toxin components in inhibiting the early stages of infection by anthrax spores. (http://www.ncbi.nlm.nih.gov/pubmed/11390699?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed) [Microbiology. 2001]
Mucosal immunization with a novel nanoemulsion-based recombinant anthrax protective antigen vaccine protects against Bacillus anthracis spore challenge. (http://www.ncbi.nlm.nih.gov/pubmed/17502384?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedarticles&logdbfrom=pubmed) [Infect Immun. 2007]
Comparative safety and efficacy against Bacillus anthracis of protective antigen and live vaccines in mice. (http://www.ncbi.nlm.nih.gov/pubmed/3148815?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedarticles&logdbfrom=pubmed) [Microb Pathog. 1988]
ReviewMolecular basis for improved anthrax vaccines. (http://www.ncbi.nlm.nih.gov/pubmed/15935874?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=4&log$=relatedreviews&logdbfrom=pubmed) [Adv Drug Deliv Rev. 2005]
Review[Vaccination strategies for anthrax prevention] (http://www.ncbi.nlm.nih.gov/pubmed/15584433?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed) [Berl Munch Tierarztl Wochenschr. 2004]

» See Reviews... (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pubmed_reviews&LinkReadableName=Related Reviews&IdsFromResult=19168734&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&log$=relatedreviews&logdbfrom=pubmed) | » See All... (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pubmed&LinkReadableName=Related Articles&IdsFromResult=19168734&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&log$=relatedarticles&logdbfrom=pubmed)

Momtezuma Tuatara
20-03-09, 05:44 PM
so how is a nano-based vaccine made?

http://www.med.umich.edu/opm/newspage/2008/nanoemulsion.htm



Nanoemulsion vaccines developed at the Michigan Nanotechnology Institute for Medicine and the Biological Sciences (http://www.nano.med.umich.edu/) 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.
A team led by U-M scientist James Baker Jr., M.D., the institute’s director, pioneered the technology, for which a patent was recently awarded to U-M.

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 interesting thing about this, is ... "How do they know that nano-based vaccines do not have some harmful effect on humans in vivo? Where are the studies? "

You can argue that this is a much more natural way of provoking the immune system to react the right way, but these sorts of remarks were made about the injectable vaccines as well.

however, nanovaccines will be just the ticket for doctors to say to parents that vaccines are "natural" now.

Momtezuma Tuatara
20-03-09, 08:30 PM
http://nano.med.umich.edu/Platforms/Adjuvant-Vaccine-Development.html

unherdof
21-03-09, 01:37 AM
I think it's pretty telling that there is a reach toward mucosal vaccination at all. This is essentially an admission of the fact that a cell-mediated immune response is preferred... yet you'll here indefinitely that the current method of delivering antigens via vaccination is the "same".

cartersmom
23-03-09, 03:00 AM
I see why they would try this. It makes sense, however I could see the primary immune system being completely destroyed this way No?

MinorityView
23-03-09, 03:25 AM
I bet people without immune systems will really need lots and lots of drugs! No?

Momtezuma Tuatara
23-03-09, 01:19 PM
I was reading another medical article on the different sorts of nano emulsions, and frankly, it's frightening...

They talk about avoiding adjuvants, like aluminium (bad thing, you know....) yet avoid making the point that the only reason they know aluminium isn't too hot, is because of recent research.

Before that, toxicity studies weren't done on aluminium, because they were presumed ipso facto, to be safe:

http://www.fda.gov/cber/minutes/tox120202.htm (http://www.fda.gov/cber/minutes/tox120202.htm)



Historically, the non-clinical safety assessment for preventive vaccines has often not included toxicity studies in animal models. This is because vaccines have not been viewed as inherently toxic, and vaccines are generally administered in limited dosages over months or even years ...

And you know, it's very important to have good clinical data and controlled clinical trials. But I think we also recognize that there are a number of things that we really need to learn more about, and certainly aluminum is one of them.




Now here we are in a situation where nano-emulsions are also, ipso facto, assumed to be safe. They always assume everything is always safe, and it's that history which shows a great big orange light to me.