Featured Research

from universities, journals, and other organizations

Route for eliciting HIV-neutralizing antibodies mapped

Date:
August 12, 2011
Source:
NIH/National Institute of Allergy and Infectious Diseases
Summary:
Researchers have traced in detail how certain powerful HIV neutralizing antibodies evolve, a finding that generates vital clues to guide the design of a preventive HIV vaccine, according to a new study.

Top: These images show three antibodies’ HIV-binding segments, which neutralize the virus. The VRC01 and VRC03 antibodies were found in the blood of an HIV-infected North American donor, while the VRC-PG04 antibody was found in the blood of an HIV-infected African donor. Bottom: Superimposing the HIV-binding segments of the three antibodies shows structural differences and similarities. The regions that are similar allow all three antibodies to bind to the same spot on the virus and to neutralize a high percentage of HIV strains from around the world.
Credit: NIAID VRC

Researchers have traced in detail how certain powerful HIV neutralizing antibodies evolve, a finding that generates vital clues to guide the design of a preventive HIV vaccine, according to a study appearing in Science Express this week. The discoveries were made by a team led by the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Related Articles


"This elegant research brings us another step closer to an HIV vaccine and establishes a potent new technique for evaluating the human immune response to experimental vaccines, not only for HIV, but for pathogens generally," said NIAID Director Anthony S. Fauci, M.D.

The new findings build on last year's discovery reported by VRC scientists of three HIV antibodies, two of which could stop more than 90 percent of known global HIV strains from infecting human cells in the laboratory. Called VRC01, VRC02 and VRC03, these antibodies were found in blood donated for NIAID studies by an HIV-infected North American known as donor 45. In the new paper, scientists report discovering antibodies similar to VRC01 in the blood of two HIV-infected Africans known as donor 74 and donor 0219.

The researchers further discovered that these VRC01-like antibodies all bind to the same spot on HIV in the same way. This suggests that an HIV vaccine should contain a protein replica of this spot, known as the CD4 binding site, to elicit antibodies as powerful as VRC01, according to the researchers. The CD4 binding site is one of the few parts of the continuously mutating virus that stays the same across HIV variants worldwide, and the virus uses this site to attach to the cells it infects.

The scientists previously found that the genes for VRC01-like antibodies undergo an unusually high number of mutations -- 70 to 90 -- between the first draft that codes for a weak antibody and the final version that codes for an antibody that can neutralize HIV. These genes lie in the DNA of immune cells called B cells.

"To make a vaccine that elicits VRC01-like antibodies, we will need to coach B cells to evolve their antibody genes along one of several pathways, which we have now identified, from infancy to a mature, HIV-fighting form," said VRC Director Gary J. Nabel, M.D., Ph.D.

To guide B cells along this extended evolutionary pathway, the scientists first needed to map the route. They began by turning to an existing technology to sequence the collection of B-cell genes that code for all the antibodies created by a person's immune system. This study marks the first time this technology, called deep sequencing, has been used to track the evolution of the antibody response to HIV at the genetic level. The NIH researchers then devised sophisticated bioinformatics techniques to decipher the large library of genetic data produced by deep sequencing.

"We found a way to read the books, or genes, in this library by defining unique characteristics of VRC01-like antibodies," said Peter Kwong, Ph.D., chief of the VRC's structural biology section and co-principal investigator of the study.

Based on their discovery of the common structure and genetic origin of the VRC01-like antibodies, the scientists devised strategies for scanning the B-cell DNA libraries of donor 45 and donor 74. From hundreds of thousands of antibody genes, the scientists first identified thousands that code for VRC01-like antibodies and then sorted these genes into family trees showing their evolution from their earliest stage into mature forms. The genes that coded for HIV neutralizing antibodies grouped together on the same branches of the trees.

Next, the researchers focused on the gene segment that codes for the part of the VRC01-like antibody that attaches to and neutralizes HIV. Examining this sequence in the genes of the newfound relatives of VRC01 revealed how the sequence changed step by step along one of a few clear paths from its original state into a mature form. A vaccine that elicits VRC01-like antibodies would need to coax the B-cell DNA of immature antibodies to evolve along one of these pathways.

The scientists now aim to create proteins they can deliver through a vaccine to serve as signposts that direct the development of B-cell DNA to produce VRC01-like antibodies.

The new research has far-reaching implications for vaccine development. "As we develop and test new HIV vaccines, it will be possible to analyze not just antibodies in the blood, but also the specific B-cell genes that are responsible for producing antibodies against HIV," said John R. Mascola, M.D., deputy director of the VRC and co-principal investigator of the study. "This information will indicate whether an investigational HIV vaccine in a preclinical or clinical trial is heading in the right direction."


Story Source:

The above story is based on materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Materials may be edited for content and length.


Journal Reference:

  1. Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O’Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused evolution of HIV-1 neutralizing antibodies revealed by crystal structures and deep sequencing. Science, 11 August 2011 DOI: 10.1126/science.1207532

Cite This Page:

NIH/National Institute of Allergy and Infectious Diseases. "Route for eliciting HIV-neutralizing antibodies mapped." ScienceDaily. ScienceDaily, 12 August 2011. <www.sciencedaily.com/releases/2011/08/110811142812.htm>.
NIH/National Institute of Allergy and Infectious Diseases. (2011, August 12). Route for eliciting HIV-neutralizing antibodies mapped. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2011/08/110811142812.htm
NIH/National Institute of Allergy and Infectious Diseases. "Route for eliciting HIV-neutralizing antibodies mapped." ScienceDaily. www.sciencedaily.com/releases/2011/08/110811142812.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Christmas Kissing Good for Health

Christmas Kissing Good for Health

Reuters - Innovations Video Online (Dec. 22, 2014) Scientists in Amsterdam say couples transfer tens of millions of microbes when they kiss, encouraging healthy exposure to bacteria. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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