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.
Dr. Mascola serves as director of the VRC, chief of the Virology Laboratory, and chief of the Humoral Immunology Section. He also holds concurrent appointments as adjunct professor of medicine at the Uniformed Services University of the Health Sciences and as a consulting physician in the division of infectious diseases at the Walter Reed National Military Medical Center. Dr. Mascola joined the VRC in October 2000 as deputy director. His research focuses on HIV humoral immune responses and vaccine design. Prior to joining the VRC, Dr. Mascola served as head of HIV prevention research in the division of retrovirology at the Walter Reed Army Institute of Research.
After graduating magna cum laude from Tufts University and earning his medical degree at Georgetown University School of Medicine, Dr. Mascola completed a residency in internal medicine and a fellowship in infectious diseases at the National Naval Medical Center, followed by a fellowship in retroviral diseases at the Walter Reed Army Institute of Research. Dr. Mascola is a Fellow of the American College of Physicians (FACP), a member of the Infectious Diseases Society of America (IDSA), and has been elected to the American Society of Clinical Investigation (ASCI) and the Association of American Physicians (AAP).
Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, Fire AZ, Roskin KM, Schramm CA, Zhang Z, Zhu J, Shapiro L; NISC Comparative Sequencing Program, Mullikin JC, Gnanakaran S, Hraber P, Wiehe K, Kelsoe G, Yang G, Xia SM, Montefiori DC, Parks R, Lloyd KE, Scearce RM, Soderberg KA, Cohen M, Kamanga G, Louder MK, Tran LM, Chen Y, Cai F, Chen S, Moquin S, Du X, Joyce MG, Srivatsan S, Zhang B, Zheng A, Shaw GM, Hahn BH, Kepler TB, Korber BT, Kwong PD, Mascola JR, Haynes BF. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013 Apr 25;496(7446):469-76.
Pancera M, Yang Y, Louder MK, Gorman J, Lu G, McLellan JS, Stuckey J, Zhu J, Burton DR, Koff WC, Mascola JR, Kwong PD. N332-directed broadly neutralizing antibodies use diverse modes of HIV-1 recognition: inferences from heavy-light chain complementation of function. PLoS One. 2013;8(2):e55701.
Joyce MG, Kanekiyo M, Xu L, Biertümpfel C, Boyington JC, Moquin S, Shi W, Wu X, Yang Y, Yang ZY, Zhang B, Zheng A, Zhou T, Zhu J, Mascola JR, Kwong PD, Nabel GJ. Outer domain of HIV-1 gp120: antigenic optimization, structural malleability, and crystal structure with antibody VRC-PG04. J Virol. 2013 Feb;87(4):2294-306.
Lingwood D, McTamney PM, Yassine HM, Whittle JR, Guo X, Boyington JC, Wei CJ, Nabel GJ. Structural and genetic basis for development of broadly neutralizing influenza antibodies. Nature. 2012 Sep 27;489(7417):566-70.
Wei CJ, Yassine HM, McTamney PM, Gall JG, Whittle JR, Boyington JC, Nabel GJ. Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure. Sci Transl Med. 2012 Aug 15;4(147):147ra114.
Cheng C, Wang L, Gall JG, Nason M, Schwartz RM, McElrath MJ, DeRosa SC, Hural J, Corey L, Buchbinder SP, Nabel GJ. Decreased pre-existing Ad5 capsid and Ad35 neutralizing antibodies increase HIV-1 infection risk in the Step trial independent of vaccination. PLoS One. 2012;7(4):e33969.
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For more information on research conducted by John R. Mascola, M.D., Ph.D. visit the Virology Core.
Last Updated March 31, 2014