Researchers from the National Institute of Allergy and Infectious Diseases (NIAID) have discovered two potent human antibodies which can neutralize and kill up to 90 percent of HIV strains from infecting people in the lab.
The two antibodies – named VRC01 and VRC02 – attach to the CD4 binding site of HIV and appear to prevent the virus from attaching to and infecting T cells.
According to the study, the researchers were able to determine the atomic-level structure of VRC01 when it’s attached to HIV, allowing them to design components of a potential vaccine that could teach the human immune system to make similar antibodies that could feasibly prevent infection by the vast majority of HIV strains worldwide.
The WHO has estimated that more than 34 million people had HIV at the end of 2010. An estimated 2.7 million people worldwide were newly infected with HIV in that year.
Led by Drs. Peter Kwong and John R. Mascola, the researchers found that the genes for VRC01-like antibodies undergo an unusually high number of mutations – 70 to 90 – between the first draft, which codes for a weak antibody, and the final version that codes for an antibody that can neutralize HIV.
Structural analysis revealed that the VRC01-like antibodies from the different donors all bind in the same way to the same spot on HIV. They attach to a molecule called GP120 in a region known as the CD4 binding site. HIV uses this site to attach to the cells it infects. It is one of the few parts of the virus that stays the same across HIV variants worldwide.
The genes for antibodies lie in the DNA of immune cells called B cells. To track the evolution of the antibody response to HIV at the genetic level, the researchers examined the B-cell DNA of 2 donors using a method called deep sequencing, along with sophisticated bioinformatics.
Among hundreds of thousands of antibody genes, the researchers identified thousands that code for VRC01-like antibodies. They then sorted these genes into family trees showing their evolution from their earliest stage into mature forms.
Next, the researchers focused on the gene segment that codes for the part of the antibody that attaches to and neutralizes HIV. They examined these sequences in detail to reveal how they changed step by step from their original state into a mature form.
“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 Dr. Gary J. Nabel, director of NIAID’s Vaccine Research Center.
The scientists now aim to create proteins that can deliver through a vaccine to serve as signposts that direct the development of B-cell DNA to produce VRC01-like antibodies. This study 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,” Mascola said.
The research was published in the online edition of the journal Science.