Featured Research

from universities, journals, and other organizations

Structure Solved By Scripps Scientists Marks Important Milestone In Effort To Develop HIV Vaccine

Date:
August 13, 2001
Source:
Scripps Research Institute
Summary:
Scientists working in The Skaggs Institute for Chemical Biology at The Scripps Research Institute (TSRI) and at the Glycobiology Institute at Oxford University in the United Kingdom, have elucidated the structure of an antibody that effectively neutralizes human immunodeficiency virus (HIV), reported in the current issue of the journal Science.

Scientists working in The Skaggs Institute for Chemical Biology at The Scripps Research Institute (TSRI) and at the Glycobiology Institute at Oxford University in the United Kingdom, have elucidated the structure of an antibody that effectively neutralizes human immunodeficiency virus (HIV), reported in the current issue of the journal Science. Designated b12, the antibody has a long finger-like region on its surface that penetrates the surface of the main viral glycoprotein gp120 on the HIV virus and prevents it from causing disease. The authors hope that the structure of this region will provide a basis for the design of effective vaccines against the HIV virus.

"A lot of people in the HIV field are excited by this structure," says Professor Ian Wilson, D. Phil., of the The Skaggs Institute and Department of Molecular Biology. "It clearly illustrates the sort of antibody you need to raise in order to have an effective vaccine against HIV."

HIV causes AIDS by binding to, entering, and, ultimately, leading to the killing of certain blood cells—distinguished by a certain protein, called CD4, that these cells carry on their surfaces. T cells and macrophages, which both carry CD4, are necessary to fight off infections by common bacteria and other pathogens, and these pathogens become potentially lethal to patients after their own immune system destroys the infected CD4 cells.

One of the most compelling medical challenges today is to develop a vaccine that will provide complete prophylactic protection to someone who is later exposed to this virus.

An important part of such a vaccine will be an effective neutralizing antibody against HIV.

Also called immunoglobins, these antibodies would be produced by the body's B cells after HIV enters the bloodstream. During such an immune response, the antibodies would circulate through the blood, and track down and kill the virus.

Normally, the antibodies that the body produces to fight HIV are ineffective because much of the surface of the virus is inaccessible.

"HIV is coated with carbohydrates," says scientist Erica Ollmann Saphire, Ph.D., who is first author on the paper. "They cloak the virus."

Even worse, antibodies mostly recognize long protein loops on the outside of the virus, and in the body HIV rapidly mutates so that these loops become unrecognizable. The antibody b12, though, appears to be effective against a wide variety of HIV isolates. This is because it binds to part of the HIV that cannot mutate—the region of the virus that must bind to CD4. The antibody neutralizes the virus, making it unable to invade cells. A further problem is that the virus sheds its cell surface gp120 and antibodies raised against this viral debris are ineffective against the intact virus. Thus, the shed viral proteins act as a decoy to divert the immune response from the virus itself.

First identified in the bone marrow of a 31-year-old male who had been HIV positive without symptoms for six years, b12 demonstrates the human immune system is capable of raising antibodies that are effective against HIV, and scientists will now be investigating the ways in which this type of immune response can be triggered.

Another notable fact about this accomplishment is that this structure is the first human antibody to be solved in its entirety. Normally, scientists only solve a piece of an antibody—the fragment at the end—because whole antibodies do not form good crystals, an important first step in solving a structure. But by working with an antibody preparation that was unusually pure, the team managed to make crystals and solve the structure.

The research article, "Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design" is authored by Erica Ollmann Saphire, Paul W.H.I. Parren, Ralph Pantophlet, Michael B. Zwick, Robyn L. Stanfield, Garrett M. Morris, Pauline M. Rudd, Raymond A. Dwek, Dennis R. Burton, and Ian A. Wilson, and appears in the August 10, 2001 issue of the journal Science.

The research was funded in part by the National Institutes of Health and The Skaggs Institute for Research.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Cite This Page:

Scripps Research Institute. "Structure Solved By Scripps Scientists Marks Important Milestone In Effort To Develop HIV Vaccine." ScienceDaily. ScienceDaily, 13 August 2001. <www.sciencedaily.com/releases/2001/08/010813081505.htm>.
Scripps Research Institute. (2001, August 13). Structure Solved By Scripps Scientists Marks Important Milestone In Effort To Develop HIV Vaccine. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2001/08/010813081505.htm
Scripps Research Institute. "Structure Solved By Scripps Scientists Marks Important Milestone In Effort To Develop HIV Vaccine." ScienceDaily. www.sciencedaily.com/releases/2001/08/010813081505.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins