In their search for new and more effective vaccines, OHSU scientists are still unraveling the intricacies of those operations of the immune system that protect us from microbial infection. By understanding the mechanisms involved with improving T cell and B cell responses to foreign antigens, we will be able to develop more effective vaccines against viruses and other microbial pathogens.
Mark Slifka, Ph.D. and his colleagues are investigating the underlying mechanisms of humoral and cell-mediated immunity against acute and chronic viral infections. This work has included developing several models of viral infection and/or vaccination in order to address basic immunological questions related to the development and maintenance of long-term protective immunity. This is collectively referred to as “immunological memory”. Dr. Slifka’s group has also developed a series of clinical studies in which they analyze immunological memory directly in human subjects. During the course of this work, they study a number of viruses including arenaviruses (lymphocytic choriomeningitis virus, LCMV), alphaviruses (chikungunya virus, Eastern-, Western-, and Venezualen equine encephalitis viruses), orthopoxviruses (vaccinia, cowpox, monkeypox, smallpox) and flaviviruses (West Nile virus, yellow fever, dengue and zika).
The combination of basic research in animal models and applied research in clinical studies involving both healthy and immunocompromised populations has provided the opportunity to better define the requirements for immunological memory and to learn how to develop more effective diagnostics and vaccine candidates.
These experiments lay the foundation for future studies in which Slifka and his team plan to develop new vaccines and determine the mechanisms involved with building strong vaccine-induced immunity. They have discovered a new hydrogen peroxide (H2O2)-based approach to vaccine development that results in safer, more effective human and animal vaccines. Dr. Slifka and his colleagues recently launched a first-in-man H2O2-based West Nile virus vaccine clinical trial. Details of the Phase I clinical trial describing HydroVax-001 West Nile virus can be found at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02337868).
Areas of interest
- Immunological memory
- Memory B cells & plasma cells
- Memory T cells
- Ph.D., UCLA School of Medicine 1996
Honors and awards
- AAAS • Robert I. Larus Award (1991)
- AAAS • Geraldine K. Lindsay Award (1991)
- AAAS • Outstanding Presentation in the Biological Sciences (1991)
- Association of Research Professors Award (1992)
- The Scripps Society of Fellows Award (1997)
- ICAAC Young Investigator Award (1998)
- OHSU Commercialization Award (2004)
- OHSU Commercialization Award (2005)
- OHSU Technology Innovation Award; Top 10 Industry Collaborations (2009)
- CHAVI Visiting Professor at Duke University Medical Center (2010)
- Visiting Professor at the Mayo Clinic (2012)
- Vaccine, Council of 100 (2013)
- Fellow of the International Society for Vaccines (2014)
Memberships and associations
- Journal of Virology, Editorial Board 2005-Present
- Journal of Immunology, Editorial Board 2006-Present
- Virology, Editorial Board 2007-Present
- Vaccine, Editorial Board 2013-Present
- npg Vaccines, Editorial Board 2016-Present
- Clinical and Vaccine Immunology, Editorial Board 2016-Present
Slifka MK, Leung DY, Hammarlund E, Raué HP, Simpson EL, Tofte S, Baig-Lewis S, David G, Lynn H, Woolson R, Hata T, Milgrom H, Hanifin J (2014). Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis. J Allergy Clin Immunol. 2014. 133(2):439-47. PMID: 24331381. PMCID: PMC3960337.
Slifka MK, Amanna I (2014). How advances in immunology provide insight into improving vaccine efficacy. Vaccine. May 23;32(25):2948-57. PMID: 24709587. PMCID: PMC4096845.
Hammarlund E, Thomas A, Poore EA, Amanna IJ, Rynko AE, Mori M, Chen Z, Slifka MK (2016). Durability of vaccine-induced immunity against tetanus and diphtheria toxins: A cross-sectional analysis. Clin Infect Dis. May 1;62(9):1111-8. PMID: 27060790.
Amanna IJ, Slifka MK (2016). Questions regarding the safety and duration of immunity following live yellow fever vaccination. Expert Rev Vaccines. 2016 Dec;15(12):1519-1533. Epub 2016 Jun 20. PMCID: PMC5171234.
Poore EA, Slifka DK, Raué HP, Thomas A, Hammarlund E, Quintel BK, Torrey LL, Slifka AM, Richner JM, Dubois ME, Johnson LP, Diamond MS, Slifka MK, Amanna IJ (2017). Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine. Vaccine. 2017 Jan 5;35(2):283-292. PMID: 27919629. PMCID: PMC5191926.
- "Dengue Serostatus and Dengue Vaccine Safety and Efficacy." The New England journal of medicine In: , Vol. 379, No. 20, 15.11.2018.
- "Heterogeneity and longevity of antibody memory to viruses and vaccines." PLoS Biology In: , Vol. 16, No. 8, e2006601, 10.08.2018.
- "Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein." Nature Microbiology In: , 01.01.2018.
- "Plasma cell survival in the absence of B cell memory." Nature Communications In: , Vol. 8, No. 1, 1781, 01.12.2017.
- "Lymphatic Vessels Balance Viral Dissemination and Immune Activation following Cutaneous Viral Infection." Cell Reports In: , Vol. 20, No. 13, 26.09.2017, p. 3176-3187.
- "Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine." Vaccine In: , Vol. 35, No. 2, 05.01.2017, p. 283-292.
- "Questions regarding the safety and duration of immunity following live yellow fever vaccination." Expert Review of Vaccines In: , Vol. 15, No. 12, 01.12.2016, p. 1519-1533.
- "Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections." Cell In: , Vol. 167, No. 3, 20.10.2016, p. 684-694.e9.
- "Alcohol intake alters immune responses and promotes CNS viral persistence in mice." Behavioural Brain Research In: , Vol. 312, 01.10.2016, p. 1-8.
- "Temporal Dynamics of CD8 T Cell Effector Responses during Primary HIV Infection." PLoS Pathogens In: , Vol. 12, No. 8, e1005805, 01.08.2016.
- "Durability of Vaccine-Induced Immunity Against Tetanus and Diphtheria Toxins : A Cross-sectional Analysis." Clinical Infectious Diseases In: , Vol. 62, No. 9, 01.05.2016, p. 1111-1118.
- "Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion." American Journal of Transplantation In: , 2016.
- "Long-Lived Plasma Cells Are Contained within the CD19CD38CD138 Subset in Human Bone Marrow." Immunity In: , Vol. 43, No. 1, 21.07.2015, p. 132-145.
- "Rat cytomegalovirus vaccine prevents accelerated chronic rejection in CMV-Naïve recipients of infected donor allograft hearts." American Journal of Transplantation In: , Vol. 15, No. 7, 01.07.2015, p. 1805-1816.
- "Cytokine-mediated activation of NK cells during viral infection." Journal of Virology In: , Vol. 89, No. 15, 2015, p. 7922-7931.
- "How advances in immunology provide insight into improving vaccine efficacy." Vaccine In: , Vol. 32, No. 25, 23.05.2014, p. 2948-2957.
- "Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis." Journal of Allergy and Clinical Immunology In: , Vol. 133, No. 2, 02.2014, p. 439-447.
- "Current trends in West Nile virus vaccine development." Expert Review of Vaccines In: , Vol. 13, No. 5, 2014, p. 589-608.
- "Vaccine-mediated immunity against dengue and the potential for long-term protection against disease." Frontiers in Immunology In: , Vol. 5, No. MAY, 195, 2014.
- "Pathophysiologic and Transcriptomic Analyses of Viscerotropic Yellow Fever in a Rhesus Macaque Model." PLoS Neglected Tropical Diseases In: , Vol. 8, No. 11, 2014.
- "Anti-inflammatory cytokines directly inhibit innate but not adaptive CD8+ T cell functions." Journal of Virology In: , Vol. 88, No. 13, 2014, p. 7474-7484.
- "T Cell Inactivation by Poxviral B22 Family Proteins Increases Viral Virulence." PLoS Pathogens In: , Vol. 10, No. 5, e1004123, 2014.
- "A cell-intrinsic requirement for NF-κB-inducing kinase in CD4 and CD8 T cell memory." Journal of Immunology In: , Vol. 191, No. 7, 01.10.2013, p. 3663-3672.
- "Editorial : Profiling senescent influenzaspecific T cells in the elderly." Journal of Leukocyte Biology In: , Vol. 93, No. 6, 01.06.2013, p. 819-821.
- "Antiviral immune response after live yellow fever vaccination of a kidney transplant recipient treated with IVIG." Transplantation In: , Vol. 95, No. 9, 15.05.2013.
- "A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal west nile virus infection in aged mice." Journal of Virology In: , Vol. 87, No. 4, 02.2013, p. 1926-1936.
- "Cytokine-Mediated Programmed Proliferation of Virus-Specific CD8+ Memory T Cells." Immunity In: , Vol. 38, No. 1, 24.01.2013, p. 131-139.
- "Characterization of CD8+ T cell function and immunodominance generated with an H2O2-inactivated whole-virus vaccie." Journal of Virology In: , Vol. 86, No. 24, 12.2012, p. 13735-13744.
- "Impact of infection or vaccination on pre-existing serological memory." Human Immunology In: , Vol. 73, No. 11, 11.2012, p. 1082-1086.
- "A Flow Cytometry-Based Assay for Quantifying Non-Plaque Forming Strains of Yellow Fever Virus." PLoS One In: , Vol. 7, No. 9, e41707, 19.09.2012.