Nanotechnology approach shows promise with vaccines

by Nathan Bomey | Ann Arbor Business Review

Thursday March 13, 2008, 3:37 AM

Robert Ramey
James Baker, founder of NanoBio.

Researchers have long believed that nanotechnology could one day target afflictions such as cold sores.

But University of Michigan scientists recently revealed two studies suggesting that nanoemulsion vaccines helped mice build up immunity to smallpox and HIV.

The technology, which is licensed through Ann Arbor-based firm NanoBio Corp., would use an oil-based emulsion administered through the nose rather than injecting patients using needles.

James Baker, director of the Michigan Nanotechnology Institute for Medicine and founder of NanoBio, said recent studies have indicated "that mucosal immunity may be very important in protecting individuals from AIDS."

In unrelated news, NanoBio announced that it may soon begin Phase 3 clinical trials on one of its topical lotions after getting positive clinical data and receiving a corresponding $10 million round of funding.

The firm, a spinout of the University of Michigan, has received an additional $10 million in equity funding from Perseus LLC - which has now contributed $30 million over the past 18 months to NanoBio. Perseus is a private equity investment firm with operations in New York City and Washington, D.C.

NanoBio recently said that Phase 2 clinical trial data on its topical lotion candidate NB-001 displayed positive indications that the therapy is ready for Phase 3 - the final stage before a drug reaches the market.

Company officials indicated that the firm would begin planning Phase 3 trials for NB-001 - a lotion that aims to treat cold sores using a nanotechnology-based lotion.
Baker recently spoke with Business Review reporter Nathan Bomey about the nanoemulsion studies. Excerpts:

Business Review: What was the key breakthrough in this news about the nanoemulsion vaccines?

Baker: We demonstrated that this (technology) can be used for almost any type of vaccine.

In addition, it can produce the type of immunity that's most desired for protection against viruses - that is cellular immunity that induces destruction of virally infected cells.

Have you known for quite some time that nanotechnology could eventually target HIV?

I think both of these vaccines are new in terms of how they are approached. No one has been able to produce a kill-virus smallpox vaccine before, and the uniqueness of the nanotechnology platform, I think, is very important to that.

The other thing was that recently there have been failures of a number of different AIDS vaccines. And also new evidence has come out that suggested that mucosal immunity may be very important in protecting individuals from AIDS. It makes sense.

So the fact that this vaccine produces not just cellular immunity but also mucosal immunity may make it more effective than some of the vaccines that have previously failed.

There are many different ideas about how to create a smallpox vaccine. What makes this one stand out?

The key here is that most of the applications we might use this vaccine in are really very different from what's going on with smallpox before.

There wasn't a risk with smallpox right now that justifies the risk of a live viral vaccine. So for things like a monkeypox outbreak or a suspected bioterrorism event, the risk of the vaccine may actually outweigh the risk from the event.

So having a vaccine that's safer than the current vaccine but is effective in preventing the infection if it were to occur is a really a change in the dynamic.

Talk about the market for nanotechnology-based technology. What is that market like right now?

Well the market is really wide open and there's a potential for incredible growth. We estimate that for some of the projects NanoBio is currently developing, they could be billion-dollar markets. NanoBio has at least three or four potential drugs for those markets. That gives you an idea of the potential for this technology.

What is the FDA approval process like for nanotechnology-based technology right now?

I think that it's essentially the same as any other vaccine, and we hope to be in people with at least one nanotechnology-based vaccine by the end of this year.

Has the FDA historically looked at nanotechnology suspiciously or do they see it as promising technology?

I think they see it as promising technology. Part of that's been because we've done our homework and we've made sure that anything we brought to the agency was well justified, and we've done appropriate efficacy and toxicity testing to justify their evaluation.

In the life sciences industry, we're seeing a lot of fragmentation with the big pharmas outsourcing a lot of their services. Do you think nanotechnology firms could be a target for acquisitions from the major pharmaceutical companies?

I think that's a good possibility. In some ways, it's been easier for them to evaluate traditional companies because they have milestones.

But for example, a company like NanoBio, which now has positive Phase 2 clinical trials, it (has) really breakthrough products based on nanotechnology (and) could easily be perceived as a takeover target.

Link to article

Contact Nathan Bomey at (734) 302-1725 or nathanb@mbusinessreview.com.

NanoBio - Nanoemulsion vaccines effective against HIV?

February 28th, 2008

Posted by Roland Piquepaille @ 10:10 am

Nanoemulsions are non-toxic lipid droplets approved for human consumption and common food substances that are defined as ‘Generally Recognized as Safe’ (GRAS) by the FDA. But they also can be used for medical applications. Researchers at the University of Michigan have developed nasal nanoemulsion vaccines for influenza which were successfully tested in animals in 2003. Now, the same team has shown that nanoemulsion vaccines are effective against smallpox and HIV — at least for mice. The scientists are using an oil-based emulsion placed in the nose instead of needles. It should take years before this technique could be approved for human usage, but it really looks promising. But read more…

You can see above how nanoemulsion particles enhance the immune response system. “Nanoemulsion particles lyse virus and incorporate viral antigens into their structure. The particles are then rapidly taken up by antigen presenting dendritic cells to enhance presentation to helper T-cells.” (Credit: NanoBio Corporation). Please note that “lysis refers to the death of a cell by breaking of the cellular membrane” (Credit: Lysis page on Wikipedia).

These research projects have been led by James Baker Jr., director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences (M-NIMBS) ans some members of his team including
Anna Bielinska, a Research Assistant Professor. For more information about this specific project, please read the Nanoemulsions page at M-NIMBS.

Here is a more detailed explanation of how nanoemulsions work. “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 could lead to an effective human vaccine against smallpox that is safer than the present live-vaccinia virus vaccine. “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.”

Regarding a possible protection about HIV, the researchers said that “the HIV nanoemulsion vaccine tested in the noses of mice in the study represents ‘a different approach in the way it produces immunity and the type of immunity produced.’ Vaccines administered in the nose are also able to induce mucosal immunity in the genital mucosa. Evidence is growing that HIV virus can infect the mucosal immune system. ‘Therefore, developing mucosal immunity may be very important for protection against HIV,’ added Baker.”

The study about a nanoemulsion vaccine protecting from smallpox has been published in Clinical and Vaccine Immunology under the name “A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine” (February 2008, p. 348-358, Vol. 15, No. 2). Here is a link to the abstract.

The other study, about a vaccine showing immunity against HIV, has been published in AIDS Research and Human Retroviruses under the name “Nasal Immunization with a Recombinant HIV gp120 and Nanoemulsion Adjuvant Produces Th1 Polarized Responses and Neutralizing Antibodies to Primary HIV Type 1 Isolates” (Volume 24, Number 2, Pages 271-281, February 2008). Here are two links to the abstract and to the full paper (PDF format, 11 pages, 217 KB).

Finally, this technology about nanoemulsion vaccines is licensed to NanoBio Corporation, “an Ann Arbor-based biotech company which Baker founded in 2000 and in which he has a financial interest.” Here are some other sources of information from NanoBio Corporation.

• their latest news release, news release named “Nasal Vaccine for Smallpox Confers High Levels of Immunity without Safety Risks” (February 26, 2008)
• a page about how their NanoStat technology works
• and a page about Mucosal-Vaccines, from which the above illustration has been picked

Sources: University of Michigan Health System news release, February 26, 2008; and various websites

http://blogs.zdnet.com/emergingtech/?p=848

US patents link
EPO patents link