Researchhttp://hdl.handle.net/1803/95712024-03-19T13:23:17Z2024-03-19T13:23:17ZNeutralization fingerprinting technology for characterizing polyclonal antibody responses to dengue vaccinesRaju, NagarajanZhan, XiaoyanDas, SubashKarwal, LovkeshDean, Hansi J.Crowe Jr, James E.Carnahan, Robert H.Georgiev, Ivelin S.http://hdl.handle.net/1803/180482023-03-02T19:28:24Z2022-12-13T00:00:00ZNeutralization fingerprinting technology for characterizing polyclonal antibody responses to dengue vaccines
Raju, Nagarajan; Zhan, Xiaoyan; Das, Subash; Karwal, Lovkesh; Dean, Hansi J.; Crowe Jr, James E.; Carnahan, Robert H.; Georgiev, Ivelin S.
Dengue is a major public health threat. There are four dengue virus (DENV) serotypes; therefore, efforts are focused on developing safe and effective tetravalent DENV vaccines. While neutralizing antibodies contribute to protective immunity, there are still important gaps in understanding of immune responses elicited by dengue infection and vaccination. To that end, here, we develop a computational modeling framework based on the concept of antibody-virus neutralization fingerprints in order to characterize samples from clinical studies of TAK-003, a tetravalent vaccine candidate currently in phase 3 trials. Our results suggest a similarity of neutralizing antibody specificities in baseline-seronegative individuals. In contrast, amplification of pre-ex-isting neutralizing antibody specificities is predicted for baseline-seropositive individuals, thus quantifying the role of immunologic imprinting in driving antibody responses to DENV vaccines. The neutralization finger-printing analysis framework presented here can contribute to understanding dengue immune correlates of protection and help guide further vaccine development and optimization.
2022-12-13T00:00:00ZBenign Neurofibroma/Schwannoma Hybrid Peripheral Nerve Sheath Tumor of the Ulnar Nerve Harboring a Metastatic Papillary Thyroid Carcinoma Deposit: A Case Report of Tumor-to-Tumor MetastasisColazo, Juan M.Perez, Alexander N.Judice, Anthony D.Quirion, JuliaPrieto-Granada, Carlos N.Holt, Ginger E.http://hdl.handle.net/1803/179392023-01-23T21:59:35Z2022-12-14T00:00:00ZBenign Neurofibroma/Schwannoma Hybrid Peripheral Nerve Sheath Tumor of the Ulnar Nerve Harboring a Metastatic Papillary Thyroid Carcinoma Deposit: A Case Report of Tumor-to-Tumor Metastasis
Colazo, Juan M.; Perez, Alexander N.; Judice, Anthony D.; Quirion, Julia; Prieto-Granada, Carlos N.; Holt, Ginger E.
A 74-year-old man with a medical history significant for papillary thyroid cancer (PTC) presented with a rapidly enlarging grape-sized mass in his right medial arm with paresthesia in the ulnar nerve distribution. Imaging was suspicious for a peripheral nerve sheath tumor (PNST), but an ultrasound-guided biopsy was equivocal. The mass was excised with final histopathology demonstrating a benign neurofibroma/schwannoma hybrid nerve sheath tumor (N/S HNST) harboring a metastatic PTC deposit, ultimately mimicking the rare glandular schwannoma subtype. Next-generation sequencing (NGS) of the lesion demonstrated somatic variants in BRAF and TERT (common in PTC) and NF2 (common in PNSTs). After excision, the patient's nerve symptoms improved. A postsurgical PET/CT scan also showed progression in the lungs/mediastinum. Due to the metastatic nature of his PTC, he was treated with 14 mg of Lenvima (lenvatinib) daily, and his PET/CT surveillance was performed at more frequent intervals. Tumor-to-tumor metastasis (TTM) is a rare occurrence. To our knowledge, this is the first case reported on PTC metastasizing into a benign (hybrid) PNST, which mimicked glandular schwannoma. Symptomatology, imaging characteristics, NGS, and histopathological characteristics that can decipher between different benign PNST subtypes (schwannoma, neurofibroma, glandular, hybrid, etc.), malignant PNSTs (MPNSTs), and TTM are described.
2022-12-14T00:00:00ZPublic Health Importance of Invasive Methicillin-sensitive Staphylococcus aureus Infections: Surveillance in 8 US Counties, 2016Jackson, Kelly A.Gokhale, Runa H.Nadle, JoelleRay, Susan M.Dumyati, GhinwaSchaffner, WilliamHam, David C.Magill, Shelley S.Lynfield, RuthSee, Isaachttp://hdl.handle.net/1803/162982022-11-09T07:09:30Z2020-03-15T00:00:00ZPublic Health Importance of Invasive Methicillin-sensitive Staphylococcus aureus Infections: Surveillance in 8 US Counties, 2016
Jackson, Kelly A.; Gokhale, Runa H.; Nadle, Joelle; Ray, Susan M.; Dumyati, Ghinwa; Schaffner, William; Ham, David C.; Magill, Shelley S.; Lynfield, Ruth; See, Isaac
Background. Public health and infection control prevention and surveillance efforts in the United States have primarily focused on methicillin-resistant Staphylococcus aureus (MRSA). We describe the public health importance of methicillin-susceptible S. aureus (MSSA) in selected communities.
Methods. We analyzed Emerging Infections Program surveillance data for invasive S. aureus (SA) infections (isolated from a normally sterile body site) in 8 counties in 5 states during 2016. Cases were considered healthcare-associated if culture was obtained >3 days after hospital admission; if associated with dialysis, hospitalization, surgery, or long-term care facility (LTCF) residence within 1 year prior; or if a central venous catheter was present <= 2 days prior. Incidence per 100 000 census population was calculated, and a multivariate logistic regression model with random intercepts was used to compare MSSA risk factors with those of MRSA.
Results. Invasive MSSA incidence (31.3/100 000) was 1.8 times higher than MRSA (17.5/100 000). Persons with MSSA were more likely than those with MRSA to have no underlying medical conditions (adjusted odds ratio [aOR], 2.06; 95% confidence interval [CI], 1.26-3.39) and less likely to have prior hospitalization (aOR, 0.70; 95% CI, 0.60-0.82) or LTCF residence (aOR, 0.37; 95% CI, 0.29-0.47). MSSA accounted for 59.7% of healthcare-associated cases and 60.1% of deaths.
Conclusions. Although MRSA tended to be more closely associated with healthcare exposures, invasive MSSA is a substantial public health problem in the areas studied. Public health and infection control prevention efforts should consider MSSA prevention in addition to MRSA.
2020-03-15T00:00:00ZBroad dengue neutralization in mosquitoes expressing an engineered antibodyCrowe, James E., Jr.http://hdl.handle.net/1803/161482020-09-24T03:06:43Z2020-01-01T00:00:00ZBroad dengue neutralization in mosquitoes expressing an engineered antibody
Crowe, James E., Jr.
Author summary With limited success of traditional vector control methods to curb dengue infections and more than half of the world's population still at risk, there is a need for novel strategies to reduce its impact on public health. Recent advances in genetic technologies has allowed for precise modifications of mosquito genome to make them resistant to infections, thus breaking the transmission cycle. Here we generated engineered Ae. aegypti mosquitoes efficiently expressing a DENV-targeting single-chain variable fragment (scFv) derived from a previously characterized broadly neutralizing human antibody, which blocked infection and transmission in these mosquitoes. To our knowledge, this is the first example of an engineered transgene capable of rendering Ae. aegypti mosquitoes 100% refractory to all four serotypes of DENV. The engineered mosquitoes, in future, could easily be paired with a gene drive, capable of spreading the transgene throughout wild disease-transmitting mosquito populations and preventing further DENV transmission. Since a number of diverse and well-characterized antibodies exist against other arboviruses (eg chikungunya and Zika, this work also provides a proof-of-concept principle for developing similar genetic strategies for reducing the impact of these arboviruses.
With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses.
Only Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://pubmed.ncbi.nlm.nih.gov/31945137/
2020-01-01T00:00:00Z