Researchers design unique method to induce immunity to certain STDs

Apr 30, 2009

Chlamydia trachomatis is the most common bacterial agent of sexually transmitted disease, accounting for more than a million reported infections in the United States each year.

Researchers at the California NanoSystems Institute (CNSI) at UCLA and the David Geffen School of Medicine at UCLA have now designed a unique method for inducing immunity to the infection. The findings could accelerate progress toward the development of a vaccine against Chlamydia trachomatis infections, which can lead to reproductive dysfunction and profound local inflammation requiring medical attention.

The researchers were able to uncover a surprising connection between vault nanoparticles and mucosal immunity. Vaults are barrel-shaped nanoscale capsules found in the cytoplasm of all mammalian cells that can be engineered to serve as potential therapeutic delivery devices.

"The primary goal of vaccines is to generate robust cell-mediated immune responses at mucosal surfaces while reducing overall inflammation caused by infection," Kelly said. "We found that vault nanoparticles containing immunogenic proteins can act as 'smart adjuvants' for inducing protective immunity at mucosal surfaces while avoiding destructive inflammation."

Adjuvants are molecular triggers that initiate vaccine responses.

Mucosal immune responses provide superior protection against disease, but there are currently no adjuvants approved by the Food and Drug Administration that are capable of stimulating cell-mediated immune responses within mucosal tissues. Mucosal surfaces are hostile environments, and immunogenic proteins require added protection for delivery to cells in order to induce immunity.

The team produced recombinant vaults through a process that involved the molecular engineering of these naturally occurring cellular structures to test the concept that vaults can have a broad nanosystems application as malleable nanocapsules.

"Our research team wanted to find out if recombinant vaults could provide such protection by encapsulating an antigen and preserving its functional characteristics, even within the cells," Kelly said.

The internal cavity of the recombinant vault nanoparticle is large enough to hold multiple immunogenic proteins, and because vaults are the size of small microbes, a vault particle containing such proteins can be easily absorbed by the targeted cells.

Vaults are being studied for use in the delivery of a range of potential therapeutics, including synthetic and natural compounds, nucleic acids, and proteins. Recombinant vaults containing proteins are easily produced, making vaults a viable vaccine delivery platform.

"Adjuvants provide the necessary assistance to vaccine preparations for promoting immunity or protection from infection by combining the vault with a part of the Chlamydia organism," Kelly said. "We were able to design a vaccine that prevented Chlamydia infection better than other designs."

The research team found that when they immunized female mice with recombinant vaults containing a component of Chlamydia and then exposed the mice to a vaginal challenge with live Chlamydia, their reproductive tracts were protected from severe bacterial infection.

The results suggest that vaults are superior adjuvants for immunization against infections largely limited to mucosal tissues.

"We are encouraged that our findings could accelerate progress toward developing a vaccine to guard against this infection," Kelly said.

The study appears in the April 30 edition of the peer-reviewed online journal PLoS ONE, published by the Public Library of Science, and is available at http://dx.plos.org/10.1371/journal.pone.0005409.

Source: University of California - Los Angeles

Explore further: Antioxidant found in grapes uncorks new targets for acne treatment

add to favorites email to friend print save as pdf

Related Stories

UCLA scientists store materials in cells' natural vaults

Mar 08, 2005

Method may offer safer way to target drugs to living cells In the realm of nanotechnology, or study of the tiny, scientists often aim to safely deliver and leave material in the human body without causing harm. A big chall ...

Mice help researchers understand chlamydia

Oct 29, 2007

Genetically engineered mice may hold the key to helping scientists from Queensland University of Technology and Harvard hasten the development of a vaccine to protect adolescent girls against the most common sexually transmitted ...

Possible Chlamydia vaccine target found

Sep 12, 2007

U.S. scientists have identified a potential target for a vaccine to fight Chlamydia -- the world's most prevalent sexually transmitted bacterial infection.

Recommended for you

Scientists discover gene controlling muscle fate

6 hours ago

Scientists at the University of New Mexico have moved a step closer to improving medical science through research involving muscle manipulation of fruit flies. They discovered in the flight muscles of Drosophila ...

Study clues to aging bone loss

6 hours ago

In Canada, bone fractures due to osteoporosis affect one in three women and one in five men over their lifetimes, costing the health care system more than $2.3 billion a year.

User comments : 0