Mark K. Slifka
In their search for new and more effective vaccines, 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 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. We have also developed a series of clinical studies in which we study immunological memory directly in human subjects. During the course of this work, we study a number of viruses including arenaviruses (lymphocytic choriomeningitis virus, LCMV), alphaviruses (chikungunya virus), flaviviruses (West Nile virus, yellow fever, and dengue), and orthopoxviruses (vaccinia, cowpox, and monkeypox). Several of these viruses cause encephalitis or meningitis (e.g., LCMV, West Nile Virus, and vaccine strains of yellow fever virus) and one of our goals is to develop better vaccines against encephalitic viruses. 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 antiviral vaccines and determine the mechanisms involved with building strong vaccine-induced immunity. These scientists have discovered a new hydrogen peroxide H2O2-based approach to vaccine production that results in a safer, more effective vaccine preparation that can be used to create better human and animal vaccines. In 2015, Dr. Slifka and his colleagues 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).
After graduating from Washington State University with a B.S. degree in microbiology and molecular biology in 1992 and from the UCLA School of Medicine with a Ph.D. in microbiology and immunology in 1996, Mark Slifka became a postdoctoral fellow in the department of neuropharmacology at the Scripps Research Institute in La Jolla. He came to OHSU as an assistant professor and to ONPRC as an affiliate assistant scientist in 2001 and was promoted to associate professor and associate scientist in 2006. Dr. Slifka was promoted to professor in 2011 and to senior scientist in 2013.
Slifka MK, Leung DY, Hammarlund E, Raue` HP, Simpson EL, Tofte S, Baig-Lewis S, David G, Lynn H, Woolson R, Hata T, Milgrom H, Hanifin J. Transcutaneous yellow fever vaccination of subjects with or with out atopic dermatitis. J Allergy Clin Immunol. 2014. 133(2):439-47. PMID: 24331381 PMCID: PMC3960337.
Slifka MK, Amanna I. How advances in immunology provide insight into improving vaccine efficacy. Vaccine. 2014. May 23:32(25)2948-57. PMID 24709587. PMCID: PMC4096845.
Freeman BE, Meyer C, Slifka MK. Anti-inflammatory cytokines directly inhibit innate but not adaptive CD8+T cell functions. Journal of Virology. 2014 Jul;88(13):7474-84. PMID 24741101. PMCID: PMC4054413.
Halliley JL, Tipton CM, Liesveld J, Rosenberg AF, Darce J, Gregoretti IV, Popova L, Kaminiski D, Fucile CF, Albizua I, Kyu S, Chiang KY, Bradley KT, Burack R, Slifka MK, Hammarlund E, Wu H, Zhoa L, Walsh EE, Falsey AR, Randall TD, Cheung WC, Sanz I, Lee FE. Long-lived Plasma Cells are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. Immunity. 2015 Jul 21;43(1):132-45. PMID: 26187412.
Amanna IJ, Raue` HP, Slifka MK. Development of a new H2O2-based vaccine platform. Nat Med. 2012 June;18(6):974-9. PMID: 22635006. PMCID:PMC3506259.
Freeman BE, Hammarlund E, Raue` HP, Slifka MK. Regulation of innate CD8+T-cell activation mediated by cytokines. Proc Natl Acad Sci USA. 2012 Jun 19;109(25):9971-6. PMID 22665806. PMCID: PMC3382521.
Amanna IJ, Hammarlund E, Lewis MW, Slifka MK. Impact of infection or vaccination on pre-existing serological memory. Hum Immunol. 2012. 73(11):1082-86. PMID 22902392. PMCID: PMC3478407.
Raue` HP, Beadling C, Haun J, Slifka MK. Cytokine-mediated programmed proliferation of virus-specific CD8(+) memory T cells. Immunity. 2013 Jan 24;38(1):131-9. PMID 23260193. PMCID: PMC3557534.
See a full listing of Dr. Slifka's publications.