Title : From Antibody to Antibodyome: Finding the Coordinates of an Effective HIV-1 Vaccine
Speaker: Tongqing Zhou，Staff Scientist, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Host: Prof. Mingyao Liu
When: 2012-12-24 14:00
Where: Conference Room 534, School of Life Sciences
Reporter introduction:
Tongqing Zhou received his Ph.D. in cell biology from the Chinese Academy of Science in 1994. From 1995 to 2001, he worked as a postdoctoral research associate at Wayne State University Medical School where he developed interest in protein crystallography and earned master’s degree in electronic and computer-controlled systems. Since he joined the Vaccine Research Center in 2001, Dr. Zhou has focused on the application of structural biology on deciphering the immune evasion mechanisms of HIV-1 virus as well as the neutralization mechanisms of broadly neutralizing antibodies.
Abstract：
Extraordinary global diversity and immune-evasion capabilities of the human immunodeficiency virus type 1 (HIV-1) have greatly hindered the development of an effective HIV-1 vaccine. However, recent studies indicate that the human immune system is capable of developing antibodies that neutralize HIV-1. About ~20% of those infected with HIV-1 develop sera with the ability to neutralize diverse strains of HIV-1 after two or more years. A number of human monoclonal antibodies have been isolated from HIV-1-infected donors that can potently neutralize circulating HIV-1 strains with target sites on both envelope glycoprotein gp120 and gp41. Vaccine development efforts are on-going with these antibodies as template. However, a lot of these recently identified broad neutralizing antibodies have at least one unusual feature that may impede antibody induction, such as long complementarity determining regions, high levels of somatic mutations, skewed or restricted gene usages as well as polyreactivity. For example, the broad and potent VRC01 class CD4-binding site antibodies utilize a common germline origin (IGHV1-2*02) for their heavy chain variable domains and require high rates of somatic mutation. Understanding of B cell ontogeny of VRC01 class antibodies is critical to the successful development of an effective vaccine that elicits VRC01 class antibodies. Combining structural biology and genetic approaches, we reveal a convergence of recognition by VRC01 class antibody heavy chains. Analysis of antibodyome generated by deep sequencing of multiple donors indicate that the generation of VR01 class antibodies may be a deterministic process, unlike most other antibodies which usually develop in stochastic ways. As essential components for the B-cell lineage-based vaccine design approach, the application of structural biology and deep sequencing enable us to elucidate antibody clonal lineages and maturation pathways. Different strategies may be needed for eliciting antibodies that develop in deterministic or stochastic pathways.