Major Areas of Research
- Combination of novel techniques for the comprehensive evaluation of CD4 T- and B-cell responses elicited by vaccination
- Influenza and HIV B-cell immunobiology
- Analysis of immune correlates associated with vaccine protection
Vaccine discovery and development requires intimate knowledge of the immune responses during infection and by in experimental immunization in suitable animal models and ultimately clinical trials. Immunological end point analyses of clinical trials at the Vaccine Research Center (VRC) take place at the NIAID Vaccine Immune T Cell, and Antibody Laboratory (NVITAL), who employ state-of-the-art, high-throughput, rigorously validated analyses for regulatory and licensure purposes. The Immunology Core (IMC) Laboratory addresses more basic hypothesis-driven analyses of clinical trials in close association with NVITAL and the Clinical Trials Core (CTC). The IMC has a number of responsibilities: 1) Answer specific immunological questions by developing and implementing novel analyses on samples from clinical trial volunteers, 2) Advance the field by contribution to the HIV Vaccine Immune Monitoring Consortium-Collaboration for AIDS Vaccine Discovery (VIMC-CAVD), 3) Work with the investigators at the VRC to screen novel immunogens capable of eliciting efficacious immune responses, 4) Collaborate with other intra- and extra-mural investigators to further hypothesis driven vaccine research.
While the IMC is continually extending the capabilities of better evaluating aspects of vaccine-elicited immunity, the current focus is upon the detailed assessment of specific B-cell responses from the perspective of enumeration, phenotype, and function. We have applied new technologies such as Fluidigm Biomark and MSD platforms for the analysis of B cell subpopulations and BCR from influenza and HIV clinical vaccine trials. In exploiting the multiplexing capacity of the MSD platform, we have identified and characterized regions within HIV envelope and influenza stem that elicit specific functional antibodies, which has furthered our knowledge in comparative immunogenicity of HIV clinical trials, HIV-specific B-cell dysfunction, and the development of a universal influenza vaccine. The goal of the IMC is to further the understanding of T- and B-cell immunobiology in order to better design efficacious vaccination strategies.
For more information on research conducted by Dr. McDermott, visit the Immunology Laboratory.
Dr. Adrian B. McDermott has more than 20 years experience as an experimental virologist and immunologist, in the fields of vaccines and HIV, including, the elucidation and characterization of T and B cell responses associated with control of replication or protection from HIV or SIV infection. During his work in pre-clinical immunology, he headed a large consortium dedicated to the investigation of factors associated with protection elicited by live attenuated SIVs; led a team that evaluated new vector platforms for delivery of T and B cell immunogens; and developed the low dose-multiple exposure SIV challenge model for the improved assessment of vaccines in the face of virus challenge. This has subsequently been refined into the commonly used acquisition model, which allows us to evaluate HIV vaccines in terms of "protection from multiple exposures" in the NHP. He obtained his Ph.D. in immunogenetics and virology, studying hepatitis B vaccines at the Royal Free Hospital, University College London. He pursued post-doctoral work at the Aaron Diamond Research Center, Rockefeller University, New York; Gladstone Institute; University of California San Francisco; and the National Primate Center, University of Wisconsin-Madison before moving to the International AIDS Vaccine Initiative as Director of Immunobiology and Vaccine Design. Dr. McDermott joined the VRC in 2011.
Whittle JR, Wheatley AK, Wu L, Lingwood D, Kanekiyo M, Ma SS, Narpala SR, Yassine HM, Frank GM, Yewdell JW, Ledgerwood JE, Wei CJ, McDermott AB, Graham BS, Koup RA, Nabel GJ. Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple Ig heavy chain lineages. J.Virol 2014 in press
McDavid A et al. Data exploration, quality control and testing in single-cell qPCR-based gene expression experiments.Bioinformatics (Oxford, England) (2013).doi:10.1093/bioinformatics/bts714
Fukazawa Y, Park H, Cameron MJ, Lefebvre F, Lum R, Coombes N, Mahyari E, Hagen SI, Bae JY, Reyes MD 3rd, Swanson T, Legasse AW, Sylwester A, Hansen SG, Smith AT, Stafova P, Shoemaker R, Li Y, Oswald K, Axthelm MK, McDermott A, Ferrari G, Montefiori DC, Edlefsen PT, Piatak M Jr, Lifson JD, Sékaly RP, Picker LJ. Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines. Nat Med. 2012 Sep 9.
McDermott AB, Koup RA. CD8(+) T cells in preventing HIV infection and disease. AIDS. 2012 Jun 19;26(10):1281-92. Review.
Yamamoto T, Johnson MJ, Price DA, Wolinsky DI, Almeida JR, Petrovas C, Nason M, Yeh WW, Shen L, Roederer M, Rao SS, McDermott AB, Lefebvre F, Nabel GJ, Haddad EK, Letvin NL, Douek DC, Koup RA. Virus inhibition activity of effector memory CD8(+) T cells determines simian immunodeficiency virus load in vaccinated monkeys after vaccine breakthrough infection. J Virol. 2012 May;86(10):5877-84.
Winstone N, Wilson AJ, Morrow G, Boggiano C, Chiuchiolo MJ, Lopez M, Kemelman M, Ginsberg AA, Mullen K, Coleman JW, Wu CD, Narpala S, Ouellette I, Dean HJ, Lin F, Sardesai NY, Cassamasa H, McBride D, Felber BK, Pavlakis GN, Schultz A, Hudgens MG, King CR, Zamb TJ, Parks CL, McDermott AB. Enhanced control of pathogenic Simian immunodeficiency virus SIVmac239 replication in macaques immunized with an interleukin-12 plasmid and a DNA prime-viral vector boost vaccine regimen. J Virol. 2011 Sep;85(18):9578-87.