Melissa Herbst-Kralovetz

Melissa Herbst-Kralovetz

Professor, Basic Medical Sciences
Associate Professor, Clinical Translational Sciences
Associate Professor, Obstetrics and Gynecology
Associate Professor, BIO5 Institute
Contact
(602) 827-2247

Research Interest

Melissa Herbst-Kralovetz, PhD is an Associate Professor in the Departments of Basic Medical Sciences and Obstetrics and Gynecology and is Director of the Women's Health Microbiome Initiative at the UA College of Medicine-Phoenix. The Herbst-Kralovetz research lab is broadly interested in understanding innate mucosal immune responses to resident bacteria, pathogens (e.g HSV-2), and microbial products at mucosal sites, including the female reproductive tract. The mucosa provides a major immune barrier (physical, biological, and chemical) to microbial insult and her lab is interested in studying the mucosal barrier function of the lower female reproductive tract and its role in host defense against infection and inflammation as well as maintaining mucosal homeostasis. Dr. Herbst-Kralovetz has a long-standing interest and background in studying infections/conditions that impact women’s health.

Publications

Doerflinger, S. Y., Winkle, S., McAllister, D., Arntzen, C., & Herbst-Kralovetz, M. -. (2013). Monoclonal antibody reactivity and specificity against GI and GII norovirus VLP. TBD.
Gardner, J. K., & Herbst-Kralovetz, M. M. (2018). IL-36g induces a transient HSV-2 resistant environment that protects against genital disease and pathogenesis. Frontiers in Immunology.
McGowin, C. L., Radtke, A. L., Abraham, K., Martin, D. H., & Herbst-Kralovetz, M. (2013). Mycoplasma genitalium infection activates cellular host defense and inflammation pathways in a 3-dimensional human endocervical epithelial cell model. The Journal of Infectious Diseases, 207(12).

Because Mycoplasma genitalium is a prevalent and emerging cause of sexually transmitted infections, understanding the mechanisms by which M. genitalium elicits mucosal inflammation is an essential component to managing lower and upper reproductive tract disease syndromes in women.

Doerflinger, S. Y., Throop, A. L., & Herbst-Kralovetz, M. M. (2014). Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. The Journal of infectious diseases, 209(12), 1989-99.

Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health.

Phoolcharoen, W., Dye, J. M., Kilbourne, J., Piensook, K., Pratt, W. D., Arntzen, C. J., Chen, Q., Mason, H. S., & Herbst-Kralovetz, M. M. (2011). A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge. Proceedings of the National Academy of Sciences of the United States of America, 108(51).

Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola virus (EBOV). The possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. We have evaluated the immunogenicity and efficacy of an EBOV vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resulting in the production of Ebola immune complexes (EICs). Although antigen-antibody immune complexes are known to be efficiently processed and presented to immune effector cells, we found that codelivery of the EIC with Toll-like receptor agonists elicited a more robust antibody response in mice than did EIC alone. Among the compounds tested, polyinosinic:polycytidylic acid (PIC, a Toll-like receptor 3 agonist) was highly effective as an adjuvant agent. After vaccinating mice with EIC plus PIC, 80% of the animals were protected against a lethal challenge with live EBOV (30,000 LD(50) of mouse adapted virus). Surviving animals showed a mixed Th1/Th2 response to the antigen, suggesting this may be important for protection. Survival after vaccination with EIC plus PIC was statistically equivalent to that achieved with an alternative viral vector vaccine candidate reported in the literature. Because nonreplicating subunit vaccines offer the possibility of formulation for cost-effective, long-term storage in biothreat reduction repositories, EIC is an attractive option for public health defense measures.