Navigation Links
Scripps research scientists devise approach that stops HIV at earliest stage of infection
Date:2/27/2008

Researchers at The Scripps Research Institute have developed a new two-punch strategy against HIV and they have already successfully tested aspects of it in the laboratory.

Their study, which appears this week in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS), may re-energize attempts to create a preventive/therapeutic vaccine against HIV, say the authors. To date, more than a dozen candidate vaccines, which have attempted to raise immunity against the spiky proteins on the viral envelope, have all failed in clinical testing.

The investigators have created devices they call glycodendrons that are designed to do two things at once: inhibit the transport of HIV from where it traditionally enters the body, preventing it from moving deeper inside where it can infect immune cells; and set up an immune antibody response to a unique carbohydrate structure on the surface of the virus.

This paper is about a new direction in HIV vaccine design, said the studys lead investigator, Scripps Research Chemistry Professor Chi-Huey Wong. Results we have so far are very promising.

To date, he says the devices have been able to stimulate the immune system of mice to induce antibodies against HIV surface glycoprotein, and, in laboratory studies, have been able to block the virus from infecting immune cells.

Targeting One Multi-Purpose Area on HIV

This new approach capitalizes on two recent findings in the field of HIV research. One is the discovery that HIV takes a Trojan horse approach to reach cells it needs to infect deep inside the human body. Scientists have described how, when the virus enters the body through sexual contact, it hitches a ride with the dendritic cells of the immune system that stand guard for invaders at the mucosal lining of tissues. The virus outsmarts these cells, however, and latches onto a particular receptor protein, known as DC-SIGN, on the dendritic cells. By sticking to these immune system fighters, HIV manages to evades immune detection while the dendritic cells travel to the ultimate goal of the virus: immune T-Cells in the lymphoid system, which HIV then invades, setting up a deadly infection that spreads.

The second discovery is that an antibody exists that can signal immune destruction of the virus. The antibody, 2G12, protects people who have it against HIV progression, but very few of those who are infected put up such an immune reaction, said the studys first author, Sheng-Kai Wang, a graduate student in Wongs laboratory. Scientists at Scripps Research have defined the details of the action of the antibody and found that recognizes a dense cluster if sugars on one region of the viruss spiky protein coatingwhich is, strikingly, the same area that HIV uses to bind to the DC-SIGN protein on dendritic cells.

Earlier, Scripps Research Professor Dennis Burton, a co-author of this study, and Wong designed and tested synthetic constructs to mimic the clusters of sugars recognized by 2G12 that could form a vaccine. Wong invented a process he calls programmable one-pot synthesis that allows him to quickly assemble many types of carbohydrate structures by placing a large number of chemical building blocks into a reaction vessel to make sequential chemical reactions.

So the Scripps Research team built a dendron structure that can bind to the DC-SIGN protein, preventing HIV from doing so, and which also mimics the sugar clusters that 2G12 binds to, prompting the immune system to produce destructive antibodies to the viral coat. The sugar structure is able to inhibit HIV from binding to DC-SIGN on dendritic cells in vitro," Wong said. "But to become a vaccine, as tested in mice, the sugar structure has to be attached to a carrier as the sugar structure alone is too small and too weak to be used as a vaccine. The sugar-carrier conjugate will also inhibit HIV from binding to DC-SIGN.

The researchers say the next step in the research is to test if the dendron antibody can target the surface coating of different kinds of HIV strains in order to evaluate the potential of the vaccine strategy.


'/>"/>
Contact: Mika Benedyk
mbenedyk@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

Related medicine news :

1. Scripps scientists peg wind as the force behind fish booms and busts
2. Scripps scientists find calcium channel blockers help normalize lysosomal storage disease cells
3. Scripps research scientists find new genetic mutation that halts the development of lupus
4. Scripps research scientists discover chemical triggers for aggression in mice
5. Scripps Health Treats More Than 160 Fire Victims at Emergency Departments Across San Diego County
6. Scripps Research scientists shed new light on how antibodies fight HIV
7. Research May Yield New Weapons Against Sepsis
8. U of Minn researchers find primary alcohol prevention programs are needed for tweens
9. Researchers collaborate to find new vaccine technology decreases E. coli in beef cattle
10. Jan Marini Skin Research Introduces Age Intervention(R) Transitions - a New Frontier in Skin Care
11. Efforts to Recruit, Retain and Research Nations Social Workers Gain Bipartisan Support in Congress
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Ellevate Network, the leading network for ... for action towards gender equality at their inaugural Summit in New York City in ... reached a social audience of over 3 million. To watch the Mobilize Women video, ...
(Date:10/13/2017)... ... October 13, 2017 , ... Talented ... the lowdown on sciatica in a new episode of "Success Files," which is ... events and innovation and investigates each subject in-depth with passion and integrity. , ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... “America On ... Christian identity. “America On The Brink” is the creation of published author, William ... several great-grandchildren. As a WWII veteran, he spent thirty years in the Navy. ...
(Date:10/12/2017)... LA (PRWEB) , ... October 12, 2017 , ... Planet ... in the U.S., announced today its plans to open a flagship location in Covington, ... occupy the former Rooms To Go store next to Office Depot in the Holiday ...
(Date:10/12/2017)... ... October 12, 2017 , ... The American College of Medical Informatics ... PhD, FACMI, during the Opening Session of AMIA’s Annual Symposium in Washington, D.C. AMIA’s ... of Morris F. Collen, a pioneer in the field of medical informatics, this prestigious ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... 2, 2017 Diplomat Pharmacy, Inc. (NYSE: ... and Consulting, LLC , and named its founder as ... in Tennessee , will operate under ... EnvoyHealth,s service offerings for health care partners to include ... "In an interoperable world, technology delivers ...
(Date:10/2/2017)... , Oct. 2, 2017  AllianceRx Walgreens Prime, ... formed by Walgreens and pharmacy benefit manager Prime Therapeutics ... new brand, which included the unveiling of new signage ... , as well as at a few other company-owned ... new brand to patients, some of whom will begin ...
(Date:10/2/2017)... , Oct. 2, 2017 The Rebound mobile ... the struggle to reverse the tide of prescription drug addiction. ... regulating their medicine intake and stepping down their dosage in ... to launch in December 2017; the first 100,000 people to ... more at http://www.rebound-solution.com/ ...
Breaking Medicine Technology: