IMMUNE RESPONSE TO INFECTION AND VACCINATION
We apply cutting-edge approaches to evaluate coronavirus and arbovirus antibody responses in those experiencing an infection and in vaccine recipients. We use the knowledge from these studies to design novel antigens for diagnostics, develop mAbs with therapeutic potential, and build prototype vaccine strategies for these viruses in collaboration with virologists, clinicians, and epidemiologists.
Selected Papers- SARS-CoV-2 mRNA vaccine induces robust specific and cross-reactive IgG and unequal neutralizing antibodies in naive and previously infected people. Narowski TM, Raphel K, Adams LE, Huang J, Vielot NA, Jadi R, de Silva AM, Baric RS, Lafleur JE, Premkumar L. Cell Rep. 2022 Feb 1;38(5):110336. doi: 10.1016/j.celrep.2022.110336. Epub 2022 Jan 20. PMID: 35090596; PMCID: PMC8769879.
- Immunological memory to common cold coronaviruses assessed longitudinally over a three-year period pre-COVID19 pandemic. Yu ED, Narowski TM, Wang E, Garrigan E, Mateus J, Frazier A, Weiskopf D, Grifoni A, Premkumar L, da Silva Antunes R, Sette A. Cell Host Microbe. 2022 Sep 14;30(9):1269-1278.e4. doi: 10.1016/j.chom.2022.07.012. Epub 2022 Jul 20. PMID: 35932763; PMCID: PMC9296686.
- The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Premkumar L, Segovia-Chumbez B, Jadi R, Martinez DR, Raut R, Markmann A, Cornaby C, Bartelt L, Weiss S, Park Y, Edwards CE, Weimer E, Scherer EM, Rouphael N, Edupuganti S, Weiskopf D, Tse LV, Hou YJ, Margolis D, Sette A, Collins MH, Schmitz J, Baric RS, de Silva AM. Sci Immunol. 2020 Jun 11;5(48):eabc8413. doi: 10.1126/sciimmunol.abc8413. PMID: 32527802; PMCID: PMC7292505.
- Zika virus infection enhances future risk of severe dengue disease. Katzelnick LC, Narvaez C, Arguello S, Lopez Mercado B, Collado D, Ampie O, Elizondo D, Miranda T, Bustos Carillo F, Mercado JC, Latta K, Schiller A, Segovia-Chumbez B, Ojeda S, Sanchez N, Plazaola M, Coloma J, Halloran ME, Premkumar L, Gordon A, Narvaez F, de Silva AM, Kuan G, Balmaseda A, Harris E. Science. 2020 Aug 28;369(6507):1123-1128. doi: 10.1126/science.abb6143. PMID: 32855339; PMCID: PMC8274975.
SERODIAGNOSTICS FOR EMERGING AND REEMERGING VIRAL PATHOGENS
In our lab, we use structure-based approaches to design novel antigens for developing simple and sample-sparing serological assays to support diagnosis, seroprevalence, and serosurveillance of emerging and re-emerging viral pathogens. We partner with clinicians and epidemiologists working in national and international research organizations to validate and implement the serological assays developed in the lab. Our laboratory is part of the NIH-funded North Carolina SeroNet Center for Excellence and Centers for Research in Emerging Infectious Diseases (CREID) Network.
Selected Papers- Novel Assay to Measure Seroprevalence of Zika Virus in the Philippines. Adams C, Jadi R, Segovia-Chumbez B, Daag J, Ylade M, Medina FA, Sharp TM, Munoz-Jordan JL, Yoon IK, Deen J, Lopez AL, de Silva AM, Premkumar L. Emerg Infect Dis. 2021 Dec;27(12):3073-3081. doi: 10.3201/eid2712.211150. PMID: 34808091; PMCID: PMC8632176.
- Single-center serological surveillance of SARS-CoV-2 in pregnant patients presenting to labor and delivery. Boggess KA, Stringer EM, Robinson WR, Munoz MC, Goodnight WH, Rahangdale L, Vora NL, Rosenbaum AJ, Bala V, Ivins A, Narowski TM, Jadi R, Premkumar L. Int J Gynaecol Obstet. 2023 Mar;160(3):874-879. doi: 10.1002/ijgo.14587. Epub 2022 Dec 8. PMID: 36416412.
- Assessment of the Field Utility of a Rapid Point-of-Care Test for SARS-CoV-2 Antibodies in a Household Cohort. Churiwal M, Lin KD, Khan S, Chhetri S, Muller MS, Tompkins K, Smith J, Litel C, Whittelsey M, Basham C, Rapp T, Cerami C, Premkumar L, Lin JT. Am J Trop Med Hyg. 2021 Nov 24;106(1):156-159. doi: 10.4269/ajtmh.21-0592. PMID: 34818625; PMCID: PMC8733539.
- SARS-CoV-2 Seroprevalence: Demographic and Behavioral Factors Associated With Seropositivity Among College Students in a University Setting. Diepstra K, Bullington BW, Premkumar L, Shook-Sa BE, Jones C, Pettifor A. J Adolesc Health. 2022 Nov;71(5):559-569. doi: 10.1016/j.jadohealth.2022.06.015. Epub 2022 Jul 4. PMID: 35985917; PMCID: PMC9377272.
- Production of the Receptor-binding Domain of the Viral Spike Proteins from 2003 and 2019 SARS CoVs and the Four Common Human Coronaviruses for Serologic Assays and Inhibitor Screening. Segovia-Chumbez B, Graham SD, Jadi R, de Silva AM, Premkumar L. Bio Protoc. 2021 May 20;11(10):e4026. doi: 10.21769/BioProtoc.4026. PMID: 34150933; PMCID: PMC8187116.
MECHANISMS OF ANTIBODY-MEDIATED VIRUS NEUTRALIZATION
In collaboration with virologists, we investigate mechanisms of antibody-mediated virus neutralization using techniques such as X-ray crystallography, cryo-electron microscopy, and site-directed mutagenesis to develop strategies for preventing and treating viral infections.
Selected Papers- Structure and neutralization mechanism of a human antibody targeting a complex Epitope on Zika virus. Adams C, Carbaugh DL, Shu B, Ng TS, Castillo IN, Bhowmik R, Segovia-Chumbez B, Puhl AC, Graham S, Diehl SA, Lazear HM, Lok SM, de Silva AM, Premkumar L. PLoS Pathog. 2023 Jan 10;19(1):e1010814. doi: 10.1371/journal.ppat.1010814. PMID: 36626401; PMCID: PMC9870165.
- A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization. Singh T, Hwang KK, Miller AS, Jones RL, Lopez CA, Dulson SJ, Giuberti C, Gladden MA, Miller I, Webster HS, Eudailey JA, Luo K, Von Holle T, Edwards RJ, Valencia S, Burgomaster KE, Zhang S, Mangold JF, Tu JJ, Dennis M, Alam SM, Premkumar L, Dietze R, Pierson TC, Ooi EE, Lazear HM, Kuhn RJ, Permar SR, Bonsignori M. Cell. 2022 Dec 8;185(25):4826-4840.e17. doi: 10.1016/j.cell.2022.10.023. Epub 2022 Nov 18. PMID: 36402135; PMCID: PMC9742325.
- Designed, highly expressing, thermostable dengue virus 2 envelope protein dimers elicit quaternary epitope antibodies. Kudlacek ST, Metz S, Thiono D, Payne AM, Phan TTN, Tian S, Forsberg LJ, Maguire J, Seim I, Zhang S, Tripathy A, Harrison J, Nicely NI, Soman S, McCracken MK, Gromowski GD, Jarman RG, Premkumar L, de Silva AM, Kuhlman B. Sci Adv. 2021 Oct 15;7(42):eabg4084. doi: 10.1126/sciadv.abg4084. Epub 2021 Oct 15. PMID: 34652943; PMCID: PMC8519570.