- PVS 3700: Emerging Infectious Diseases
- PVS 5632: Vaccines: Mechanisms of Immune Protection
Development of a Vaccine and Therapeutic Antibody for Community-Acquired Pneumonia
Mycoplasma pneumoniae is a human respiratory pathogen and the etiological agent of many cases of bronchitis and community-acquired pneumonia. Infection with this bacterium can also cause and/or exacerbate other diseases, including asthma. Diagnosis is difficult as most medical laboratories do not screen for this pathogen, given that quick and inexpensive tests are not readily available. Common first-line β-lactam antibiotics are ineffective at treating M. pneumoniae infection as this bacterium lacks a cell wall. Consequently, this pathogen is often overlooked during diagnosis of affected individuals, and common treatments do not target the source of the disease. This results in considerable economic and societal hardships due to lost and ineffective work/school time, making this pathogen a burden to public health. Unfortunately, several vaccine trials conducted in military personnel during the 1960s using inactivated bacteria resulted in variable efficacy, and in some instances vaccination appeared to exacerbate disease upon subsequent challenge with virulent M. pneumoniae. We are working with the Geary lab in Pathobiology to overcome this problem and rationally design a new M. pneumoniae vaccine that lacks the safety issues that have plagued the field for decades. We are also optimizing the formulation of a monoclonal antibody that has been shown to be useful for treatment against M. pneumoniae infection.
Development of a Vaccine for Chronic Respiratory Disease of Chickens
Mycoplasma gallisepticum is a respiratory pathogen of chickens that causes substantial losses in they layer and broiler industries. Industry currently utilizes live attenuated strains of the bacterium, which are either over-attenuated and produce weak immunity or under-attenuated and pose a safety threat to other gallinaceous birds such as turkeys. Killed bacterin vaccines also tend to produce immunity that is very short-lived. We are working with the Geary Lab in Pathobiology to use our knowledge about the pathogenesis of this bacterium to rationally design a new subunit vaccine that is both safe and efficacious.
Utilization of a Pulsatile Release Microneedle Patch for Single Administration of Vaccines Against Infectious Diseases
We are collaborating with Thanh Nguyen's lab in Engineering/Institute for Materials Science to develop a pulsatile release microneedle patch that mimics multiple injections to replace booster shots for vaccines. We are using this platform to develop vaccines for COVID-19, the Pneumococcus (Streptococcus pneumoniae), Influenza, and Rabies. With this platform we can easily deliver polysaccharide, protein, and RNA vaccines into the skin.
Therapeutic Intervention of Asthma and Other Inflammatory Conditions Using Novel Nanoparticle Delivery Systems and Gene Silencing Molecules
We are collaborating with Jessica Rouge's lab in Chemistry to develop micelle-based nanoparticles that deliver DNAzymes and siRNAs to knock down genes that are important for inflammatory conditions such as Asthma.
Improvement of Vaccines and Immunotherapeutics for Exotic Viruses and Foreign Animal Diseases
We are working collaboratively with Teresa de los Santo's lab at Plum Island Animal Disease Center to use our understanding of viral evolution and immunity broaden responses to Adenovirus-vectored vaccines against Foot and Mouth Disease virus in pigs. We are also using the Adenovirus system to develop new antiviral agents expressing porcine interferon stimulated genes.
- Gavitt TD, Hartmann AK, Sawant SS, Mara AB, Szczepanek SM, Rouge JL. "A GATA3 Targeting Nucleic Acid Nanocapsule for in vivo Gene Regulation in Asthma." ACS Nano. 2021 Jun 23. doi: 10.1021/acsnano.0c07781.
- Tran KTM, Gavitt TD, Farrell NJ, Curry EJ, Mara AB, Patel A, Brown L, Kilpatrick S, Piotrowska R, Mishra N, Szczepanek SM, Nguyen TD. "Transdermal microneedles for the programmable burst release of multiple vaccine payloads." Nat Biomed Eng. 2020 Nov 23. doi: 10.1038/s41551-020-00650-4.
- Mara AB, Gavitt TD, Tulman ER, Geary SJ, Szczepanek SM. "Lipid moieties of Mycoplasma pneumoniae lipoproteins are the causative factor of vaccine-enhanced disease." NPJ Vaccines. 2020 Apr 8;5:31.
- Canter JA, Tulman ER, Beaudet J, Lee DH, May M, Szczepanek SM, Geary SJ. "Transcriptional and Pathological Host Responses to Coinfection with Virulent or Attenuated Mycoplasma gallisepticum and Low-Pathogenic Avian Influenza A Virus in Chickens." Infect Immun. 2019 Dec 17;88(1).
- Fernandez-Sainz I, Gavitt TD, Koster M, Ramirez-Medina E, Rodriguez YY, Wu P, Silbart LK, de Los Santos T, Szczepanek SM. "The VP1 G-H loop hypervariable epitope contributes to protective immunity against Foot and Mouth Disease Virus in swine." Vaccine. 2019 Jun 6;37(26):3435-3442.
- Jiang C, Gavitt TD, Szczepanek SM. "House Dust Mite Induced Allergic Lung Inflammation is Not Exacerbated in Sickle Cell Disease Mice." Int Arch Allergy Immunol. [in press].
- Licitra D, Quinn DP, Reeder JE, Gavitt T, Dickson J, Hess B, Mangold BJ, Tuttle AD, Rosas-Rosas A, Frasca Jr. S, Szczepanek SM. "Snake Fungal Disease in Colubridae Snakes in Connecticut, 2015-2017" J. Wildl Dis. [in press].
- Roberts S, Metzger DW, Szczepanek SM. “Influenza Vaccination Protects Against Pandemic H1N1 Infection in Sickle Cell Disease Mice.” Viral Immunol. 2018 Apr 24.
- Cotte C, Szczepanek SM. "Peritoneal B-1b and B-2 B-cells confer long-term protection from pneumococcal serotype 3 infection after vaccination with Prevnar-13 and are defective in sickle cell disease mice." Vaccine. 2017 Jun 16;35(28):3520-3522.
- Beaudet J, Tulman ER, Pflaum K, Liao X, Kutish GF, Szczepanek SM, Silbart LK, Geary SJ. "Transcriptional Profiling of the Chicken Tracheal Response to Virulent Mycoplasma gallisepticum Strain Rlow." Infect Immun. 2017 Sep 20;85(10).
- Szczepanek SM, Roberts S, Rogers K, Cotte C, Adami AJ, Bracken SJ, Salmon S, Secor Jr. ER, Thrall RS, Andemariam B, Metzger DW. “Poor Long-term Efficacy of Prevnar-13 in Sickle Cell Disease Mice is Associated with an Inability to Sustain Pneumococcal-specific Antibody Titers”. PLoS One. Feb 24, 2016. PMID:26910228
- Bracken SJ, Adami AJ, Szczepanek SM, Ehsan M, Natarajan P, Guernsey LA, Rafti E, Matson AP, Schramm CM, Thrall RS. “Long-term exposure to house dust mite antigen leads to suppression of allergic airway sisease sespite persistent lung inflammation”. Int Arch Allergy Immunol. 2015;166(4):243-58. PMID:25924733
- Spotlight Article: Szczepanek SM, Boccaccio M, Pflaum K, Liao X, Geary SJ. “Hydrogen Peroxide Production from Glycerol Metabolism is Dispensable for the Virulence of Mycoplasma gallisepticum in the Tracheas of Chickens” Infect Immun. 2014 Dec; 82(12):4915-4920. PMID:25156740
- Secor ER Jr., Szczepanek SM, Matson A, Rafti E, Guernsey L, Natarajan P, McNamera JT, Schramm CM, Thrall RS, Silbart LK. “Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells”. 2013;2013:702196. PMCID: PMC3870104
- Bautista EJ, Zinski J, Szczepanek SM, Johnson E, Tulman ER, Ching W, Geary SJ, Srivastava R. “Semi-automated curation of metabolic models via flux balance analysis: a case study with Mycoplasma gallisepticum”. PLoS Comput Biol. 2013 Sept;9(9):e1003208. PMCID: PMC3764002
- Szczepanek SM, Secor ER Jr., Bracken SJ, Guernsey L, Rafti E, Matson A, Thrall RS, Andemariam B. “Transgenic Sickle Cell Disease Mice have High Mortality and Dysregulated Immune Responses After Vaccination”.Pediatr Res. 2013 Aug;74(2):141-7. PMID:23728384
- Szczepanek SM, McNamara JT, Secor ER, Natarajan P, Guernsey LA, Miller L, Ballesteros E, Jellison E, Thrall RS, Andemariam B. “Splenic Morphologic Alterations are Accompanied by Altered Baseline Immunity in a Mouse Model of Sickle Cell Disease”. Am J Pathol. 2012. 181(5):1725-34. PMCID: PMC3483810
- Secor ER, Szczepanek SM, Singh A, Guernsey L, Natarajan P, Rezaul K, Han DK, Thrall RS, Silbart LK. “LC-MS/MS Identification of a Bromelain Peptide Biomarker from Ananas comosus Merr”. 2012;2012:548486. PMCID: PMC3467939
- Tulman ER, Liao X, Szczepanek SM, Ley DH, Kutish GF, Geary SJ. “Extensive variation in surface lipoprotein gene content in a novel Mycoplasma gallisepticum strain associated with the North American house finch epizootic”. Microbiology 2012. 158(Pt 8):2073-88. PMID: 22628486
- Szczepanek SM, Barrette RW, Rood D, Alejo D, Silbart LK. “Xenoepitope Substitution Avoids Deceptive Imprinting and Broadens the Immune Response to Foot-and-Mouth Disease Virus”. Clin Vaccine Immunol. 2012. 19(4):461-7. PMCID: PMC3318270
- Szczepanek SM, Majumder S, Sheppard, ES, Liao X, Rood D, Tulman ER, Wyand S, Krause DC, Silbart LK, Geary SJ. “Vaccination of BALB/c Mice with an Avirulent Mycoplasma pneumoniae P30 Mutant Results in Disease Exacerbation Upon Challenge with a Virulent Strain”. Infect Immun. 2012. 80(3):1007-14. PMCID: PMC3294651
- May M, Szczepanek SM, Frasca S. Jr., Gates AE, Demcovitz D, Moneypenny C, Brown DR, Geary, SJ. “Effect of Sialidase Knockout and Complementation on Mycoplasma gallisepticum Cytadherence and Virulence”.Vet Micro. 2012. 157(1-2):91-5. PMID: 22197303
- Challa S, Szczepanek SM, Rood D, Barrette RW, Silbart LK. “Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity Against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs”. Advances in Virology. 2011; 2011:713769. PMCID: PMC3265312
- Barrette RW, Szczepanek SM, Rood D, Challa S, Avery N, Vajdy M, Kramer E, Rodriguez L, Silbart LK. “Use of inactivated E. coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine”. Clin Vaccine Immunol. 2011 Nov;18(11):1996-8. PMID:21918121
- Szczepanek SM, Frasca S Jr., Schumacher VL, Liao X, Padula M, Djordjevic SP, Geary SJ. “Identification of Lipoprotein MslA as a Neoteric Virulence Factor of Mycoplasma gallisepticum”. Infect Immun. 2010 78(8):3475-83. PMCID: PMC2916287
- Szczepanek SM, Tulman ER, Gorton TS, Liao X, Lu Z, Zinski J, Aziz F, Frasca S Jr., Kutish GF, Geary SJ. “Comparative Genomic Analyses of Attenuated Strains of Mycoplasma gallisepticum”. Infect Immun. 2010 78(4):1760-71. PMCID: PMC2849401
Non-peer-reviewed Publications and Book Chapters
- "Marine Disease Ecology" - Behringer DC - Editor. Chapter: Diagnosing Marine Diseases; Frasca S Jr., Gast B, Bogomolin A, Szczepanek SM. 1st ed., 2020. Oxford University Press. Oxford, UK.
- “Mollicutes: Molecular Biology and Pathogenicity” – Browning GF - Editor. Chapter: Host Immune Responses to Mycoplasmas; Szczepanek SM & Silbart LK. 2nd ed., 2014, Caister Academic Press. NY, NY.
- Szczepanek SM and Geary SJ. “Mycoplasma gallisepticum Hydrogen Peroxide-Induced Cytotoxicity and Virulence: Lack of Correlation in the Natural Host”. [Published with Spotlight Article #12]. Infect Immun. 2014 Dec; 82(12):4914.
- Szczepanek SM and Secor ER Jr. “Echinacea; Have Translational Research Outcomes Altered the Way You Prescribe this Antibacterial and Immune-modulating Phytotherapeutic?”. Naturopathic Doctor. 2013, Feb.
- UConn Today. August 2021. Tiny Bubbles: Treating Asthma with Gene Silencing Nanocapsules
- UConn Today. November 2020. Research Proves Viability of Injection-free Microneedle Technology for Single-Administration of Vaccines - UConn Today
- CT Health I-Team. October 2020. http://c-hit.org/2020/10/05/coronavirus-conversation-why-the-pandemic-matters-in-the-2020-election/
- Uconn Today. June 2020. https://today.uconn.edu/2020/06/popular-class-covid-19-available-free-uconn-alumni/
- UConn Today. June 2020. https://today.uconn.edu/2020/06/uconn-researchers-overcome-vexing-problem-vaccine-research
- Hartford Business Journal. May 2020. https://www.hartfordbusiness.com/article/uconn-course-on-pandemic-is-most-popular-in-universitys-history
- UConn Today. April 2020. https://today.uconn.edu/2020/04/pandemic-prompts-largest-class-uconn-history/
- The Day. April 2020. https://www.theday.com/article/20200411/NWS01/200419883
- UConn Today. April 2020. https://today.uconn.edu/2020/04/uconn-students-watching-learning-pandemic/
- Naturally@UConn. May 2018. https://naturally.uconn.edu/2018/05/08/course-provides-sweeping-look-at-rise-in-infectious-diseases/
- USDA Press Release. April 2017. https://nifa.usda.gov/announcement/foot-and-mouth-disease-research-reveals-new-insights
- The Daily Campus. Feburary 2016. http://dailycampus.com/stories/2016/2/15/climate-change-raises-the-risk-of-zika-and-other-diseases-scientists-say
- USDA Press Release. August 2015. http://nifa.usda.gov/press-release/usda-invests-276-million-projects-address-food-security-hunger-through-improved-animal
- Naturally@UConn. August 2015. http://naturally.uconn.edu/2015/08/25/szczepanek/
- UConn Today. June 2015. http://today.uconn.edu/2015/06/mers-should-we-be-worried/
- Naturally@UConn. January 2015. http://naturally.uconn.edu/2015/01/28/meet-new-faculty-member-steven-szczepanek/