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2. COVID-19 vaccination elicits an evolving, cross-reactive antibody response to epitopes conserved with endemic coronavirus spike proteins.

Author

Elko, Evan A, Nelson, Georgia A, Mead, Heather L, Kelley, Erin J, Carvalho, Sophia T, Sarbo, Nathan G, Harms, Caroline E, Le Verche, Virginia, Cardoso, Angelo A, Ely, Jennifer L, Boyle, Annalee S, Piña, Alejandra, Henson, Sierra N, Rahee, Fatima, Keim, Paul S, Celona, Kimberly R, Yi, Jinhee, Settles, Erik W, Bota, Daniela A, Yu, George C, Morris, Sheldon R, Zaia, John A, Ladner, Jason T, and Altin, John A

Subjects
Humans, Antibodies, Viral, Epitopes, Vaccination, Antibody Formation, Pandemics, Spike Glycoprotein, Coronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, 2019-nCoV Vaccine mRNA-1273, CP: Immunology, CP: Microbiology, multiplexed serology, vaccination, Immunization, Prevention, Emerging Infectious Diseases, Genetics, Vaccine Related, Biodefense, Pneumonia & Influenza, Infectious Diseases, Biotechnology, Pneumonia, Lung, Infection, Good Health and Well Being, Biochemistry and Cell Biology, Medical Physiology
Abstract

The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naive to SARS-CoV-2; however, almost all have previously encountered other coronaviruses (CoVs), and the role of this immunity in shaping the vaccine response remains uncharacterized. Here, we use longitudinal samples and highly multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later time points. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.

Published
2022

3. Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection

Author

Dong, Wenjuan, Wang, Jing, Tian, Lei, Zhang, Jianying, Settles, Erik W., Qin, Chao, Steinken-Kollath, Daniel R., Itogawa, Ashley N., Celona, Kimberly R., Yi, Jinhee, Bryant, Mitchell, Mead, Heather, Jaramillo, Sierra A., Lu, Hongjia, Li, Aimin, Zumwalt, Ross E., Dadwal, Sanjeet, Feng, Pinghui, Yuan, Weiming, Whelan, Sean P. J., Keim, Paul S., Barker, Bridget Marie, Caligiuri, Michael A., and Yu, Jianhua

Published
2023
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6. Domestic canines do not display evidence of gut microbial dysbiosis in the presence of Clostridioides (Clostridium) difficile, despite cellular susceptibility to its toxins

Author

Stone, Nathan E., Nunnally, Amalee E., Jimenez, Victor, Jr., Cope, Emily K., Sahl, Jason W., Sheridan, Krystal, Hornstra, Heidie M., Vinocur, Jacob, Settles, Erik W., Headley, Kyle C., Williamson, Charles H.D., Rideout, Jai Ram, Bolyen, Evan, Caporaso, J. Gregory, Terriquez, Joel, Monroy, Fernando P., Busch, Joseph D., Keim, Paul, and Wagner, David M.

Published
2019
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7. Coccidioides posadasii and SARS-CoV-2 Co-infection in the K18-hACE2 Transgenic Mouse Model

Author

Kollath, Daniel, primary, Grill, Francisca, additional, Itogawa, Ashley, additional, Fabio-Braga, Ana, additional, Morales, Matthew, additional, Shepardson, Kelly, additional, Bryant, Mitchell, additional, Yi, Jinhee, additional, Ramsey, Marieke, additional, Luberto, Emily, additional, Celona, Kimberly R., additional, Settles, Erik W., additional, Lake, Douglas, additional, Keim, Paul, additional, and Barker, Bridget, additional

Published
2023
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8. Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis

Author

Settles, Erik W., primary, Sonderegger, Derek, additional, Shannon, Austin B., additional, Celona, Kimberly R., additional, Lederer, Rachel, additional, Yi, Jinhee, additional, Seavey, Courtney, additional, Headley, Kyle, additional, Mbegbu, Mimi, additional, Harvey, Maxx, additional, Keener, Mitch, additional, Allender, Chris, additional, Hornstra, Heidie, additional, Monroy, Fernando P., additional, Woerle, Celeste, additional, Theobald, Vanessa, additional, Mayo, Mark, additional, Currie, Bart J., additional, and Keim, Paul, additional

Published
2023
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9. NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates

Author

Celona, Kimberly R., primary, Shannon, Austin B., additional, Sonderegger, Derek, additional, Yi, Jinhee, additional, Monroy, Fernando P., additional, Allender, Christopher, additional, Hornstra, Heidie, additional, Barnes, Mary B., additional, Didier, Elizabeth S., additional, Bohm, Rudolf P., additional, Phillippi-Falkenstein, Kathrine, additional, Sanford, Daniel, additional, Keim, Paul, additional, and Settles, Erik W., additional

Published
2023
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10. Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants

Author

Zarn, Katherine E., primary, Jaramillo, Sierra A., additional, Zapata, Anthony R., additional, Stone, Nathan E., additional, Jones, Ashley N., additional, Nunnally, Haley E., additional, Settles, Erik W., additional, Ng, Ken, additional, Keim, Paul S., additional, Knudsen, Steen, additional, Nuijten, Patricia M., additional, Tijsma, Aloys S. L., additional, and French, Christopher T., additional

Published
2022
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12. COVID-19 vaccination recruits and matures cross-reactive antibodies to conserved epitopes in endemic coronavirus Spike proteins

Author

Elko, Evan, primary, Nelson, Georgia A, additional, Mead, Heather L, additional, Kelley, Erin J, additional, Verche, Virginia Le, additional, Cardoso, Angelo A, additional, Ely, Jennifer L, additional, Boyle, Annalee S, additional, Piña, Alejandra, additional, Henson, Sierra N, additional, Rahee, Fatima, additional, Keim, Paul S, additional, Celona, Kimberly R, additional, Yi, Jinhee, additional, Settles, Erik W, additional, Yu, George C, additional, Morris, Sheldon R, additional, Zaia, John A, additional, Ladner, Jason T, additional, and Altin, John A, additional

Published
2022
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13. Expanding the Burkholderia pseudomallei Complex with the Addition of Two Novel Species: Burkholderia mayonis sp. nov. and Burkholderia savannae sp. nov.

Author

Hall, Carina M., primary, Baker, Anthony L., additional, Sahl, Jason W., additional, Mayo, Mark, additional, Scholz, Holger C., additional, Kaestli, Mirjam, additional, Schupp, James, additional, Martz, Madison, additional, Settles, Erik W., additional, Busch, Joseph D., additional, Sidak-Loftis, Lindsay, additional, Thomas, Astrid, additional, Kreutzer, Lisa, additional, Georgi, Enrico, additional, Schweizer, Herbert P., additional, Warner, Jeffrey M., additional, Keim, Paul, additional, Currie, Bart J., additional, and Wagner, David M., additional

Published
2022
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14. Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants

Author

Zarn, Katherine E, primary, Jaramillo, Sierra A, additional, Zapata, Anthony R, additional, Stone, Nathan E, additional, Jones, Ashley N, additional, Nunnally, Haley E, additional, Settles, Erik W, additional, Ng, Ken, additional, Keim, Paul S, additional, Knudsen, Steen, additional, Nuijten, Patricia M, additional, Tijsma, Aloys SI, additional, and French, Christopher T, additional

Published
2021
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15. FXa cleaves the SARS-CoV-2 spike protein and blocks cell entry to protect against infection with inferior effects in B.1.1.7 variant

Author

Dong, Wenjuan, primary, Wang, Jing, additional, Tian, Lei, additional, Zhang, Jianying, additional, Mead, Heather, additional, Jaramillo, Sierra A., additional, Li, Aimin, additional, Zumwalt, Ross E., additional, Whelan, Sean P.J., additional, Settles, Erik W., additional, Keim, Paul S., additional, Barker, Bridget Marie, additional, Caligiuri, Michael A., additional, and Yu, Jianhua, additional

Published
2021
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16. Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

Author

Sun, Yaping, primary, Dong, Wenjuan, additional, Tian, Lei, additional, Rao, Youliang, additional, Qin, Chao, additional, Jaramillo, Sierra A., additional, Settles, Erik W., additional, Ma, Shoubao, additional, Zhang, Jianying, additional, Yu, Kang, additional, Xu, Bo, additional, Yan, Jiazhuo, additional, Ma, Rui, additional, Li, Zhuo, additional, Dadwal, Sanjeet S., additional, Barker, Bridget M., additional, Keim, Paul S., additional, Feng, Pinghui, additional, Caligiuri, Michael A., additional, and Yu, Jianhua, additional

Published
2021
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17. Stenoparib, an Inhibitor of Cellular Poly(ADP-Ribose) Polymerase, Blocks Replication of the SARS-CoV-2 and HCoV-NL63 Human Coronaviruses In Vitro

Author

Stone, Nathan E., primary, Jaramillo, Sierra A., additional, Jones, Ashley N., additional, Vazquez, Adam J., additional, Martz, Madison, additional, Versluis, Lora M., additional, Raniere, Marlee O., additional, Nunnally, Haley E., additional, Zarn, Katherine E., additional, Nottingham, Roxanne, additional, Ng, Ken R., additional, Sahl, Jason W., additional, Wagner, David M., additional, Knudsen, Steen, additional, Settles, Erik W., additional, Keim, Paul, additional, and French, Christopher T., additional

Published
2021
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18. Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerase (PARP), blocks replication of the SARS-CoV-2 human coronavirus in vitro

Author

Stone, Nathan E., primary, Jaramillo, Sierra A., additional, Jones, Ashley N., additional, Vazquez, Adam J., additional, Martz, Madison, additional, Versluis, Lora M., additional, Raniere, Marlee O., additional, Nunnally, Haley E., additional, Zarn, Katherine E., additional, Nottingham, Roxanne, additional, Sahl, Jason W., additional, Wagner, David M., additional, Knudsen, Steen, additional, Settles, Erik W., additional, Keim, Paul S., additional, and French, Christopher T., additional

Published
2020
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20. Caprine humoral response to Burkholderia pseudomallei antigens during acute melioidosis from aerosol exposure

Author

Yi, Jinhee, primary, Simpanya, Mukoma F., additional, Settles, Erik W., additional, Shannon, Austin B., additional, Hernandez, Karen, additional, Pristo, Lauren, additional, Keener, Mitchell E., additional, Hornstra, Heidie, additional, Busch, Joseph D., additional, Soffler, Carl, additional, Brett, Paul J., additional, Currie, Bart J., additional, Bowen, Richard A., additional, Tuanyok, Apichai, additional, and Keim, Paul, additional

Published
2019
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21. Caprine humoral response to Burkholderia pseudomallei antigens during acute melioidosis from aerosol exposure

Author

Yi, Jinhee, primary, Simpanya, Mukoma F., additional, Settles, Erik W., additional, Shannon, Austin B., additional, Hernandez, Karen, additional, Pristo, Lauren, additional, Keener, Mitchell E., additional, Hornstra, Heidie, additional, Busch, Joseph D., additional, Soffler, Carl, additional, Brett, Paul J., additional, Currie, Bart J., additional, Bowen, Richard A., additional, Tuanyok, Apichai, additional, and Keim, Paul, additional

Published
2018
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22. Phylogeographic, genomic, and meropenem susceptibility analysis of Burkholderia ubonensis

Author

Price, Erin P., primary, Sarovich, Derek S., additional, Webb, Jessica R., additional, Hall, Carina M., additional, Jaramillo, Sierra A., additional, Sahl, Jason W., additional, Kaestli, Mirjam, additional, Mayo, Mark, additional, Harrington, Glenda, additional, Baker, Anthony L., additional, Sidak-Loftis, Lindsay C., additional, Settles, Erik W., additional, Lummis, Madeline, additional, Schupp, James M., additional, Gillece, John D., additional, Tuanyok, Apichai, additional, Warner, Jeffrey, additional, Busch, Joseph D., additional, Keim, Paul, additional, Currie, Bart J., additional, and Wagner, David M., additional

Published
2017
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23. Burkholderia humptydooensis sp. nov., a New Species Related to Burkholderia thailandensis and the Fifth Member of the Burkholderia pseudomallei Complex

Author

Tuanyok, Apichai, primary, Mayo, Mark, additional, Scholz, Holger, additional, Hall, Carina M., additional, Allender, Christopher J., additional, Kaestli, Mirjam, additional, Ginther, Jennifer, additional, Spring-Pearson, Senanu, additional, Bollig, Molly C., additional, Stone, Joshua K., additional, Settles, Erik W., additional, Busch, Joseph D., additional, Sidak-Loftis, Lindsay, additional, Sahl, Jason W., additional, Thomas, Astrid, additional, Kreutzer, Lisa, additional, Georgi, Enrico, additional, Gee, Jay E., additional, Bowen, Richard A., additional, Ladner, Jason T., additional, Lovett, Sean, additional, Koroleva, Galina, additional, Palacios, Gustavo, additional, Wagner, David M., additional, Currie, Bart J., additional, and Keim, Paul, additional

Published
2017
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31. Toxoplasma gondiiUpregulates Interleukin-12 To Prevent Plasmodium berghei-Induced Experimental Cerebral Malaria

Author

Settles, Erik W., Moser, Lindsey A., Harris, Tajie H., and Knoll, Laura J.

Abstract

ABSTRACTA chronic infection with the parasite Toxoplasma gondiihas previously been shown to protect mice against subsequent viral, bacterial, or protozoal infections. Here we have shown that a chronic T. gondiiinfection can prevent Plasmodium bergheiANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. Treatment with soluble T. gondiiantigens (STAg) reduced parasite sequestration and T cell infiltration in the brains of P. berghei-infected mice. Administration of STAg also preserved blood-brain barrier function, reduced ECM symptoms, and significantly decreased mortality. STAg treatment 24 h post-P. bergheiinfection led to a rapid increase in serum levels of interleukin 12 (IL-12) and gamma interferon (IFN-?). By 5 days after P. bergheiinfection, STAg-treated mice had reduced IFN-? levels compared to those of mock-treated mice, suggesting that reductions in IFN-? at the time of ECM onset protected against lethality. Using IL-10- and IL-12ßR-deficient mice, we found that STAg-induced protection from ECM is IL-10 independent but IL-12 dependent. Treatment of P. berghei-infected mice with recombinant IL-12 significantly decreased parasitemia and mortality. These data suggest that IL-12, either induced by STAg or injected as a recombinant protein, mediates protection from ECM-associated pathology potentially through early induction of IFN-? and reduction in parasitemia. These results highlight the importance of early IL-12 induction in protection against ECM.

Published
2013
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32. Whole-genome sequencing of Helicobacter pylori isolates from Native American gastric biopsy specimens.

Author

Celona K, Williamson CHD, Dholakia R, Sahl JW, Monroy FP, and Settles EW

Abstract

Helicobacter pylori infection has been linked to gastrointestinal diseases including gastric cancer. High rates of H. pylori infection and gastric cancer have been reported in indigenous populations within the United States. We report whole-genome sequencing of three H . pylori isolates originating from Native American patients presenting with gastric disease., Competing Interests: The authors declare no conflict of interest.

Published
2024
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33. COVID-19 vaccination recruits and matures cross-reactive antibodies to conserved epitopes in endemic coronavirus Spike proteins.

Author

Elko EA, Nelson GA, Mead HL, Kelley EJ, Le Verche V, Cardoso AA, Ely JL, Boyle AS, Piña A, Henson SN, Rahee F, Keim PS, Celona KR, Yi J, Settles EW, Yu GC, Morris SR, Zaia JA, Ladner JT, and Altin JA

Abstract

The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Most vaccinated subjects are naïve to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes and in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes showed a delayed but progressive increase following vaccination, we observed distinct kinetics for the endemic CoV homologs at two conserved sites in Spike S2: these became detectable sooner, and decayed at later timepoints. Using homolog-specific depletion and alanine-substitution experiments, we show that these distinctly-evolving specificities result from cross-reactive antibodies as they mature against rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.

Published
2022
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34. FXa cleaves the SARS-CoV-2 spike protein and blocks cell entry to protect against infection with inferior effects in B.1.1.7 variant.

Author

Dong W, Wang J, Tian L, Zhang J, Mead H, Jaramillo SA, Li A, Zumwalt RE, Whelan SPJ, Settles EW, Keim PS, Barker BM, Caligiuri MA, and Yu J

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human natural defense mechanisms against SARS-CoV-2 are largely unknown. Serine proteases (SPs) including furin and TMPRSS2 cleave SARS-CoV-2 spike protein, facilitating viral entry. Here, we show that FXa, a SP for blood coagulation, is upregulated in COVID-19 patients compared to non-COVID-19 donors and exerts anti-viral activity. Mechanistically, FXa cleaves the SARS-CoV-2 spike protein, which prevents its binding to ACE2, and thus blocks viral entry. Furthermore, the variant B.1.1.7 with several mutations is dramatically resistant to the anti-viral effect of FXa compared to wild-type SARA-CoV-2 in vivo and in vitro . The anti-coagulant rivaroxaban directly inhibits FXa and facilitates viral entry, whereas the indirect inhibitor fondaparinux does not. In a lethal humanized hACE2 mouse model of SARS-CoV-2, FXa prolonged survival while combination with rivaroxaban but not fondaparinux abrogated this protection. These preclinical results identify a previously unknown SP function and associated anti-viral host defense mechanism and suggest caution in considering direct inhibitors for prevention or treatment of thrombotic complications in COVID-19 patients., Competing Interests: DECLARATION OF INTERESTS No author has a direct conflict of interest relevant to this research to declare.

Published
2021
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35. Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression.

Author

Sun Y, Dong W, Tian L, Rao Y, Qin C, Jaramillo SA, Settles EW, Ma S, Zhang J, Yu K, Xu B, Yan J, Ma R, Li Z, Dadwal SS, Barker BM, Keim PS, Feng P, Caligiuri MA, and Yu J

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response., One Sentence Summary: A herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression.

Published
2021
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