Croyle, Maria A., Ph.D.
Vaccination Strategies for Rapid Induction of Immunity Against Dangerous Pathogens
The ability of human adenoviruses to induce strong innate and adaptive immune responses makes them powerful adjuvants that facilitate the immune response against an encoded antigen. Recombinant adenoviruses have been shown to elicit significant immune responses to bacterial (anthrax, plague), viral (Hepatitis C, Rabies, SARS) and tumour-associated antigens. While these results are encouraging, immunity eventually develops against the adenovirus capsid proteins. This severely reduces the immunogenicity of Ad-based vaccines in mice, primates and humans. This problem is also significant since a large portion of the Western world has marked levels of anti-adenovirus serotype 5 (Ad5) antibodies and is also prominent in developing regions of the world, where many of these vaccines are needed. Thus, assessment of the impact of pre-existing immunity on immune protection and alternative vaccination strategies may be needed for successful use of many adenovirus-based vaccines.
Work in the Croyle lab addresses this important issue by developing novel delivery methods through various mucosal routes to effectively bypass pre-existing immunity against otherwise potent recombinant adenoviral vaccine carriers. Many of these delivery strategies are amenable to single dose and self-dosing regimens without the need of booster vaccinations or professional medical personnel for administration. Several studies are carried out with collaborators from the University of Texas Medical Branch in Galveston National Laboratory (challenge studies) and the University of Pennsylvania (primate immunology).
Project Funding: Past and Present
UT Undergraduate Research Fellowships
Richardson, J.S., Yao, M.K., Tran, K.N., Croyle, M.A., Strong, J.E., Feldmann, H., and Kobinger, G.P. Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine. 2009 PLoS ONE. 4(4):e5308.
Croyle, M., Patel, A., Tran, K., Gray, M., Zhang, Y., Strong, J., Feldmann, H., and Kobinger, G.P. Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves The Immune Response In Mice. 2008 PLoS One. 3(10):e3548.
Patel, A., Zhang, Y., Croyle, M., Gray, M., Strong, J., Feldmann, H., Wilson, J.M. and Kobinger, G.P. Mucosal Delivery of Adenovirus-Based Vaccine Protects Against Ebola Virus Infection. 2007 J. Infect. Dis. 196(Suppl. 2):S413-S420.
Choi, J.H., Schafer, S.C., Kobinger, G.P., Freiberg, A., and Croyle, M.A. 2011 A Single Sublingual Dose of an Adenovirus-Based Vaccine Induces Antigen-Specific Immune Responses and Protects Mice From Lethal Ebola Infection Molec. Therapy (in review)
Richardson, J.S., Dekker. J.D., Croyle, M.A. and Kobinger, G.P. Recent Advances in Ebola Vaccine Development. 2010 Human Vaccines 6(6):439-449.
Recent Presentations at National and International Meetings
Richardson, J.S., Yao, M.K., Tran, K.N., Croyle, M.A., Strong, J.E., Feldmann, H., and Kobinger, G.P. Improved Efficacy of an Adenovirus-Based Ebola Vaccine Through Optimized Antigenic Expression: Lessons Learned from the DNA Vaccine Community
Williamsburg Bioprocessing Foundation Viral Vectors and Vaccines Conference. Austin, Texas October 28-31, 2007.
Maria A. Croyle, Invited speaker. "Mucosal Vaccination with an Adenovirus-Based Ebola Vaccine."
Ninth Annual Meeting American Association Of Gene Therapy, Baltimore, M.D. May 31-June 4, 2006.
Croyle, M. A., Feldmann, H., Jones, S. J., Wilson, J. M. and Kobigner G. P. Nasal Delivery of Adenovirus Expressing the Ebola Glycoprotein Protects Mice Against Ebola Virus in the Presence of Pre-Existing Immunity to the Vaccine Carrier
College of Pharmacy
The University of Texas
2409 University Ave.
Austin, TX, USA
Email Address: pharmacy
Dr. Bill Williams has been named editor-in-chief of AAPS PharmSciTech, the online research journal of the American Association of Pharmaceutical Scientists.