Melissa Herbst-Kralovetz
Associate Professor, BIO5 Institute
Associate Professor, Basic Medical Sciences
Associate Professor, Clinical Translational Sciences
Associate Professor, Obstetrics and Gynecology
Primary Department
Department Affiliations
(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

Łaniewski, P., & Herbst-Kralovetz, M. M. (2018). Chapter 52: Vagina. Encyclopedia of Reproduction.

Chapter within the Encyclopedia of Reproduction

Hjelm, B. E., Kilbourne, J., & Herbst-Kralovetz, M. M. (2013). TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines. Human vaccines & immunotherapeutics, 10(3).

Virus-like particles (VLPs) are an active area of vaccine research, development and commercialization. Mucosal administration of VLPs provides an attractive avenue for delivery of vaccines with the potential to produce robust immune responses. Nasal and oral delivery routes are particularly intriguing due to differential activation of mucosa-associated lymphoid tissues. We compared both intranasal and oral administration of VLPs with a panel of toll-like receptor (TLR) agonists (TLR3, 5, 7, 7/8, and 9) to determine the mucosal adjuvant activity of these immunomodulators. We selected Norwalk virus (NV) VLPs because it is an effective model antigen and an active area of research and commercialization. To prioritize these adjuvants, VLP-specific antibody production in serum (IgG, IgG1, IgG2a), vaginal lavages (IgG, IgA), and fecal pellets (IgA) were measured across a longitudinal timeseries in vaccinated mice. Additional distal mucosal sites (nasal, brochoalveolar, salivary, and gastrointestinal) were evaluated for VLP-specific responses (IgA). Intranasal co-delivery of VLPs with TLR7 or TLR9 agonists produced the most robust and broad-spectrum immune responses, systemically and at distal mucosal sites inducing VLP-specific antibodies at all sites evaluated. In addition, these VLP-specific antibodies blocked binding of NV VLPs to histo-blood group antigen (H type 1), supporting their functionality. Oral administration and/or other TLR agonists tested in the panel did not consistently enhance VLP-specific immune responses. This study demonstrates that intranasal co-delivery of VLPs with TLR7 or TLR9 agonists provides dose-sparing advantages for induction of specific and functional antibody responses against VLPs (i.e., non-replicating antigens) in the respiratory, gastrointestinal, and reproductive tract.

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.