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- COVID-19 point-of-care tests can identify low-antibody individuals: In-depth immunoanalysis of boosting benefits in a healthy cohort. Mallory M, Munt JE, Narowski TM, Castillo I, Cuadra E, Pisanic N, Fields P, Powers JM, Dickson A, Harris R, Wargowsky R, Moran S, Allabban A, Raphel K, McCaffrey TA, Brien JD, Heaney CD, Lafleur JE, Baric RS, Premkumar L. Sci Adv. 2024 Jun 14;10(24):eadi1379. doi: 10.1126/sciadv.adi1379. Epub 2024 Jun 12. PMID: 38865463; PMCID: PMC11168476.
- Serotype-specific epidemiological patterns of inapparent versus symptomatic primary dengue virus infections: a 17-year cohort study in Nicaragua. Bos S, Zambrana JV, Duarte E, Graber AL, Huffaker J, Montenegro C, Premkumar L, Gordon A, Kuan G, Balmaseda A, Harris E. Lancet Infect Dis. 2024 Oct 25:S1473-3099(24)00566-8. doi: 10.1016/S1473-3099(24)00566-8. Epub ahead of print. PMID: 39489898.
- 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.
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- Multiplex sample-sparing assay for detecting type-specific antibodies to Zika and dengue viruses: an assay development and validation study. Hein LD, Castillo IN, Medina FA, Vila F, Segovia-Chumbez B, Muñoz-Jordán JL, Whitehead SS, Adams LE, Paz-Bailey G, de Silva AM, Premkumar L. Lancet Microbe. 2024 Dec 24:100951. doi: 10.1016/j.lanmic.2024.07.014. Epub ahead of print. PMID: 39730005.
- High transmission of endemic human coronaviruses before and during the COVID-19 pandemic in adolescents in Cebu, Philippines. Joseph JO, Ylade M, Daag JV, Aogo R, Crisostomo MV, Mpingabo P, Premkumar L, Deen J, Katzelnick LC. BMC Infect Dis. 2024 Sep 27;24(1):1042. doi: 10.1186/s12879-024-09672-8. PMID: 39333882; PMCID: PMC11430261.
- 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.
ANTIBODY-MEDIATED VIRUS PROTECTION AND DISEASE
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.
- 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.
- Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination. Voss WN, Mallory MA, Byrne PO, Marchioni JM, Knudson SA, Powers JM, Leist SR, Dadonaite B, Townsend DR, Kain J, Huang Y, Satterwhite E, Castillo IN, Mattocks M, Paresi C, Munt JE, Scobey T, Seeger A, Premkumar L, Bloom JD, Georgiou G, McLellan JS, Baric RS, Lavinder JJ, Ippolito GC. Cell Rep Med. 2024 Aug 20;5(8):101668. doi: 10.1016/j.xcrm.2024.101668. Epub 2024 Aug 1. PMID: 39094579; PMCID: PMC11384961.
- Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination. Adams LE, Leist SR, Dinnon KH 3rd, West A, Gully KL, Anderson EJ, Loome JF, Madden EA, Powers JM, Schäfer A, Sarkar S, Castillo IN, Maron JS, McNamara RP, Bertera HL, Zweigert MR, Higgins JS, Hampton BK, Premkumar L, Alter G, Montgomery SA, Baxter VK, Heise MT, Baric RS.. Cell Rep. 2023 Apr 25;42(4):112326. doi: 10.1016/j.celrep.2023.112326. Epub 2023 Mar 30. PMID: 37000623; PMCID: PMC10063157.