Biography
Dr. Shelly Krebs received her Ph.D. from Dartmouth Medical School within the department of Microbiology and Immunology studying virulence factors of Vibrio cholerae. She transitioned to studying HIV when she was awarded an Emerging Infectious Disease Fellowship from the CDC and APHL as a postdoctoral fellow. With interests in HIV vaccination, she performed a second postdoctoral fellowship at the Oregon National Primate Research Center using protein scaffolds to display conserved HIV epitopes as a novel vaccine strategy. She joined MHRP in 2012 to study the development of HIV-specific B cell responses resulting from different vaccination strategies. Using similar techniques, her work as expanded beyond HIV, and into studying B cell responses resulting from infection and vaccination to other emerging pathogens such as Zika, dengue, and now SARS-CoV-2.
Research
Eliciting strong, persistent, functional antibody responses has been a major challenge for vaccine design for HIV and other infectious diseases, and the pathways that lead to durable responses remain unclear. Knowing that measuring the characteristics of antibodies alone is not enough to determine the mechanism of how functional antibodies are elicited, Dr. Krebs’s work has focused on studying the activation, differentiation and memory recall responses of antigen-specific B cells that lead to protective, durable antibodies. Understanding how individuals naturally develop effective antibody responses will lead to exploiting these characteristics in the design of immunogens for effective vaccine strategies. For example, knowing how the germline BCRs initially engage the HIV Envelope that lead to broad neutralizing antibodies has shepherded the design of immunogens capable of binding and activating these B cell lineages.
The antibody repertoire, with its exceptional diversity, provides an individual’s collective humoral response following vaccination or infection. The Krebs laboratory isolates monoclonal antibodies encoded on B cell receptors (BCRs), which provide vital information on the targeting and function the responding B cells. From the initial interaction between the antigen and the naïve B cell to somatic hypermutation in germinal centers, critical insights are gained by tracking the ontogeny of antigen-specific B cell lineages that lead to protective antibody responses. In addition, monoclonal antibodies are explored for their use as clinical tools for prophylaxis or treatment of disease.
Dr. Krebs’s research interests also include understanding the role of immune activation in disease progression. Inflammatory soluble factors that contribute to immune activation are predictive of disease progression in the absence of antiretroviral therapy (ART). However, even in the presence of ART and suppressed HIV viral load, life expectancy remains reduced compared to uninfected individuals; immune activation has been shown to be a major contributor of the increased non-AIDS morbidity and mortality. Her laboratory is interested in defining the events leading to elevated immune activation and how inflammatory soluble factors can be used to predict viral load rebound in HIV cure strategies.
Selected Publications
Lewitus E, Townsley SM, Li Y, Donofrio GC, Dearlove BL, Bai H, Sanders-Buell E, O'Sullivan AM, Bose M, Kibuuka H, Maganga L, Nitayaphan S, Sawe FK, Eller LA, Michael NL, Polonis VR, Ake JA, Vasan S, Robb ML, Tovanabutra S, Krebs SJ, Rolland M. HIV-1 infections with multiple founders associate with the development of neutralization breadth. PLoS Pathog. 2022 Mar 18;18(3):e1010369. doi: 10.1371/journal.ppat.1010369. PMID: 35303045; PMCID: PMC8967031.
Dussupt V, Sankhala RS, Mendez-Rivera L, Townsley SM, Schmidt F, Wieczorek L, Lal KG, Donofrio GC, Tran U, Jackson ND, Zaky WI, Zemil M, Tritsch SR, Chen WH, Martinez EJ, Ahmed A, Choe M, Chang WC, Hajduczki A, Jian N, Peterson CE, Rees PA, Rutkowska M, Slike BM, Selverian CN, Swafford I, Teng IT, Thomas PV, Zhou T, Smith CJ, Currier JR, Kwong PD, Rolland M, Davidson E, Doranz BJ, Mores CN, Hatziioannou T, Reiley WW, Bieniasz PD, Paquin-Proulx D, Gromowski GD, Polonis VR, Michael NL, Modjarrad K, Joyce MG, Krebs SJ. Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations. Nat Immunol. 2021 Dec;22(12):1503-1514. doi: 10.1038/s41590-021-01068-z. Epub 2021 Oct 29. PMID: 34716452.
Hastie KM, Li H, Bedinger D, Schendel SL, Dennison SM, Li K, Rayaprolu V, Yu X, Mann C, Zandonatti M, Diaz Avalos R, Zyla D, Buck T, Hui S, Shaffer K, Hariharan C, Yin J, Olmedillas E, Enriquez A, Parekh D, Abraha M, Feeney E, Horn GQ; CoVIC-DB team1, Aldon Y, Ali H, Aracic S, Cobb RR, Federman RS, Fernandez JM, Glanville J, Green R, Grigoryan G, Lujan Hernandez AG, Ho DD, Huang KA, Ingraham J, Jiang W, Kellam P, Kim C, Kim M, Kim HM, Kong C, Krebs SJ, Lan F, Lang G, Lee S, Leung CL, Liu J, Lu Y, MacCamy A, McGuire AT, Palser AL, Rabbitts TH, Rikhtegaran Tehrani Z, Sajadi MM, Sanders RW, Sato AK, Schweizer L, Seo J, Shen B, Snitselaar JL, Stamatatos L, Tan Y, Tomic MT, van Gils MJ, Youssef S, Yu J, Yuan TZ, Zhang Q, Peters B, Tomaras GD, Germann T, Saphire EO. Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study. Science. 2021 Oct 22;374(6566):472-478. doi: 10.1126/science.abh2315. Epub 2021 Sep 23. PMID: 34554826.
Townsley SM, Donofrio GC, Jian N, Leggat DJ, Dussupt V, Mendez-Rivera L, Eller LA, Cofer L, Choe M, Ehrenberg PK, Geretz A, Gift S, Grande R, Lee A, Peterson C, Piechowiak MB, Slike BM, Tran U, Joyce MG, Georgiev IS, Rolland M, Thomas R, Tovanabutra S, Doria-Rose NA, Polonis VR, Mascola JR, McDermott AB, Michael NL, Robb ML, Krebs SJ. B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies. Cell Host Microbe. 2021 Apr 14;29(4):564-578.e9. doi: 10.1016/j.chom.2021.01.016. Epub 2021 Mar 3. PMID: 33662277; PMCID: PMC8245051.
Dussupt V, Modjarrad K, Krebs SJ. Landscape of Monoclonal Antibodies Targeting Zika and Dengue: Therapeutic Solutions and Critical Insights for Vaccine Development. Front Immunol. 2021 Feb 4;11:621043. doi: 10.3389/fimmu.2020.621043. PMID: 33664734; PMCID: PMC7921836.
Dussupt V, Sankhala RS, Gromowski GD, Donofrio G, De La Barrera RA, Larocca RA, Zaky W, Mendez-Rivera L, Choe M, Davidson E, McCracken MK, Brien JD, Abbink P, Bai H, Bryan AL, Bias CH, Berry IM, Botero N, Cook T, Doria-Rose NA, Escuer AGI, Frimpong JA, Geretz A, Hernandez M, Hollidge BS, Jian N, Kabra K, Leggat DJ, Liu J, Pinto AK, Rutvisuttinunt W, Setliff I, Tran U, Townsley S, Doranz BJ, Rolland M, McDermott AB, Georgiev IS, Thomas R, Robb ML, Eckels KH, Barranco E, Koren M, Smith DR, Jarman RG, George SL, Stephenson KE, Barouch DH, Modjarrad K, Michael NL, Joyce MG, Krebs SJ. Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor. Nat Med. 2020 Feb;26(2):228-235. doi: 10.1038/s41591-019-0746-2. Epub 2020 Feb 3. PMID: 32015557; PMCID: PMC7018608.
Mdluli T, Jian N, Slike B, Paquin-Proulx D, Donofrio G, Alrubayyi A, Gift S, Grande R, Bryson M, Lee A, Dussupt V, Mendez-Riveria L, Sanders-Buell E, Chenine AL, Tran U, Li Y, Brown E, Edlefsen PT, O'Connell R, Gilbert P, Nitayaphan S, Pitisuttihum P, Rerks-Ngarm S, Robb ML, Gramzinski R, Alter G, Tovanabutra S, Georgiev IS, Ackerman ME, Polonis VR, Vasan S, Michael NL, Kim JH, Eller MA, Krebs SJ, Rolland M. RV144 HIV-1 vaccination impacts post-infection antibody responses. PLoS Pathog. 2020 Dec 8;16(12):e1009101. doi: 10.1371/journal.ppat.1009101. Erratum in: PLoS Pathog. 2021 Mar 2;17(3):e1009386. PMID: 33290394; PMCID: PMC7748270.
Krebs SJ, Kwon YD, Schramm CA, Law WH, Donofrio G, Zhou KH, Gift S, Dussupt V, Georgiev IS, Schätzle S, McDaniel JR, Lai YT, Sastry M, Zhang B, Jarosinski MC, Ransier A, Chenine AL, Asokan M, Bailer RT, Bose M, Cagigi A, Cale EM, Chuang GY, Darko S, Driscoll JI, Druz A, Gorman J, Laboune F, Louder MK, McKee K, Mendez L, Moody MA, O'Sullivan AM, Owen C, Peng D, Rawi R, Sanders-Buell E, Shen CH, Shiakolas AR, Stephens T, Tsybovsky Y, Tucker C, Verardi R, Wang K, Zhou J, Zhou T, Georgiou G, Alam SM, Haynes BF, Rolland M, Matyas GR, Polonis VR, McDermott AB, Douek DC, Shapiro L, Tovanabutra S, Michael NL, Mascola JR, Robb ML, Kwong PD, Doria-Rose NA. Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual. Immunity. 2019 Mar 19;50(3):677-691.e13. doi: 10.1016/j.immuni.2019.02.008. Epub 2019 Mar 12. PMID: 30876875; PMCID: PMC6555550.
Teigler JE, Leyre L, Chomont N, Slike B, Jian N, Eller MA, Phanuphak N, Kroon E, Pinyakorn S, Eller LA, Robb ML, Ananworanich J, Michael NL, Streeck H, Krebs SJ; RV254/RV217 study groups. Distinct biomarker signatures in HIV acute infection associate with viral dynamics and reservoir size. JCI Insight. 2018 May 17;3(10):e98420. doi: 10.1172/jci.insight.98420. PMID: 29769442; PMCID: PMC6018979.
Complete List of Published Work:
https://www.ncbi.nlm.nih.gov/myncbi/1BMOFVl6aXkgbc/bibliography/public/