John R. Mascola, M.D.
Director, Vaccine Research Center
Chief, Virology Laboratory
Major Areas of Research
- HIV immunogen and vaccine design
- Identification and characterization of broadly neutralizing HIV-1 antibodies
- Induction of broadly neutralizing, cross protective antibodies against influenza virus
The research efforts of the Virology Laboratory (VL) focus on understanding the cellular and molecular regulation of viral gene expression, HIV replication, entry into the cell, development of improved HIV envelope immunogens, optimization of immune responses to gene-based vaccination, and correlates of immune protection, with the goal of developing rationally designed vaccines against HIV, influenza, Ebola/Marburg, and other emerging and re-emerging infectious diseases. Various elements of vaccine design and delivery, including optimization of vector and protein design, adjuvants, dosing, and methods and routes of delivery, are studied. Other areas of research address mechanisms of viral gene regulation, assembly of viruses, viral cell interactions, and insight into the regulation of eukaryotic gene expression.
The VL is developing active and passive approaches for HIV vaccine development. For active approaches, the VRC continues to focus on critical issues in HIV-1 immunogen and vaccine design. The VRC has increased its major efforts on isolating broadly neutralizing mAbs, identifying and characterizing the structures of vulnerable viral epitopes, and designing immunogens to elicit potent, broadly neutralizing antibodies against HIV-1. In the realm of passive immunity, parallel efforts are underway to understand the ability of broadly neutralizing antibodies to confer passive protection by direct administration or via gene-based antibody expression. Building upon its work with VRC01, the VL has isolated multiple anti-CD4 binding site antibodies and resolved the structural identity of several HIV-1 epitopes. This structural biology work continues to drive the VRC’s approach of targeted design of active vaccine immunogens. Research on the role of cellular immunity in active immunization, its influence on humoral immunity, and the ability of CD8 cells to prevent infection is also ongoing.
The VRC is strongly emphasizing the development of novel influenza vaccines, with particular emphasis on developing a “universal” flu vaccine. The influenza research group has expanded its efforts to develop gene-based prime-boost immunization against influenza viruses and develop new vaccine strategies to induce broadly neutralizing, cross protective antibodies against influenza virus. Development of new vaccine candidates and new vector systems for antigen delivery, viral vector construction and development, structure-based protein immunogen design, and evaluation of vaccine candidates for their effectiveness in inducing potent and broad immune responses in different animal models and in human clinical trials are all important aspects of the goals of the influenza research group.