Croyle, Maria A., Ph.D.
Associate Professor
PHR 4.214D
512-471-1972
macroyle@mail.utexas.edu

Research Interests

Modification of the Adenovirus Capsid Promotes the Expansion of CD8+ Effector/Effector Memory T Cells Isolated from the Spleen. From Joe Dekker, ICMB Graduate Student

Some Formulations Improve the Cytotoxic T Cell Response Against the Transgene Cassette Elicited by Adenovirus-Based Vaccines. From Joe Dekker, ICMB Graduate Student

We are developing a vaccine against Ebola in collaboration with Gary Kobinger at the Public Health Agency of Canada. The vaccine consists of the DNA sequence for the Ebola glycoprotein encoded in a recombinant adenovirus serotype 5 vector. This vector is amplified for in vivo studies on human 293 cells.

Systemic (Panel A) and Mucosal (Panel B) T Cell Responses 14 Days after Administration of PLGA Microspheres From Jin Huk Choi, Pharmaceutics Graduate Student

Pre-Existing Immunity Does not Compromise the Cellular Immune Response by Either Nasal (I.N.) or Oral (P.O.) Vaccination (Panel A), but Does Affect the B Cell Response (Panel B) when an Unformulated Recombinant Adenovirus-Based Vaccine is Given Orally. From Croyle et al. (2009) PLoS One.

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 Public Health Agency of Canada LINK (challenge studies) and the University of Pennsylvania LINK (primate immunology).

Project Funding: Past and Present
National Institutes of Health U01 (NIAID)        

Immunobiosciences, Inc.                                     

UT Undergraduate Research Fellowships

Recent Publications

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.

Recent Presentations at National and International Meetings

Twelfth Annual Meeting American Association of Gene Therapy, San Diego, C.A.  May 27-30, 2009.

Dekker, J.D., Choi, J.H., Nash, E. E., Gray, M., Richardson, J. S., Kobigner G. P., Putche, T.P., and Croyle, M. A. An In Vitro and In Vivo Strategy for Optimization of a Recombinant Adenovirus-Based Ebola Vaccine for Nasal Administration

Choi, J.H., Dekker, J.D., and Croyle, M. A. Development of a Recombinant Adenovirus-Based Ebola Vaccine for Oral Administration

International Society of DNA Vaccines Annual Meeting, Las Vegas, N.V.  December 9-11, 2008.

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