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. To view Dr. Krebs's work at the Emerging Infectious Diseases Branch at WRAIR, click here.
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.
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. PubMed PMID: 32015557; PubMed Central PMCID: PMC7018608.
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. PubMed PMID: 30876875; PubMed Central PMCID: PMC6555550.
Rantalainen K, Berndsen ZT, Antanasijevic A, Schiffner T, Zhang X, Lee WH, Torres JL, Zhang L, Irimia A, Copps J, Zhou KH, Kwon YD, Law WH, Schramm CA, Verardi R, Krebs SJ, Kwong PD, Doria-Rose NA, Wilson IA, Zwick MB, Yates JR 3rd, Schief WR, Ward AB. HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies. Cell Rep. 2020 Apr 28;31(4):107583. doi: 10.1016/j.celrep.2020.107583. PubMed PMID: 32348769; PubMed Central PMCID: PMC7196886.
Crowell TA, Colby DJ, Pinyakorn S, Sacdalan C, Pagliuzza A, Intasan J, Benjapornpong K, Tangnaree K, Chomchey N, Kroon E, de Souza MS, Tovanabutra S, Rolland M, Eller MA, Paquin-Proulx D, Bolton DL, Tokarev A, Thomas R, Takata H, Trautmann L, Krebs SJ, Modjarrad K, McDermott AB, Bailer RT, Doria-Rose N, Patel B, Gorelick RJ, Fullmer BA, Schuetz A, Grandin PV, O'Connell RJ, Ledgerwood JE, Graham BS, Tressler R, Mascola JR, Chomont N, Michael NL, Robb ML, Phanuphak N, Ananworanich J. Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet HIV. 2019 May;6(5):e297-e306. doi: 10.1016/S2352-3018(19)30053-0. Epub 2019 Apr 15. PubMed PMID: 31000477; PubMed Central PMCID: PMC6693657.
Hellmuth J, Slike BM, Sacdalan C, Best J, Kroon E, Phanuphak N, Fletcher JLK, Prueksakaew P, Jagodzinski LL, Valcour V, Robb M, Ananworanich J, Allen IE, Krebs SJ, Spudich S. Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma. J Infect Dis. 2019 Nov 6;220(12):1885-1891. doi: 10.1093/infdis/jiz030. PubMed PMID: 30668739; PubMed Central PMCID: PMC6833977.
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. Distinct biomarker signatures in HIV acute infection associate with viral dynamics and reservoir size. JCI Insight. 2018 May 17;3(10). doi: 10.1172/jci.insight.98420. eCollection 2018 May 17. PubMed PMID: 29769442; PubMed Central PMCID: PMC6018979.
Sereti I, Krebs SJ, Phanuphak N, Fletcher JL, Slike B, Pinyakorn S, O'Connell RJ, Rupert A, Chomont N, Valcour V, Kim JH, Robb ML, Michael NL, Douek DC, Ananworanich J, Utay NS. Persistent, Albeit Reduced, Chronic Inflammation in Persons Starting Antiretroviral Therapy in Acute HIV Infection. Clin Infect Dis. 2017 Jan 15;64(2):124-131. doi: 10.1093/cid/ciw683. Epub 2016 Oct 12. PubMed PMID: 27737952; PubMed Central PMCID: PMC5215214.
Krebs SJ, Ananworanich J. Immune activation during acute HIV infection and the impact of early antiretroviral therapy. Curr Opin HIV AIDS. 2016 Mar;11(2):163-72. doi: 10.1097/COH.0000000000000228. Review. PubMed PMID: 26599167.
Krebs SJ, Slike BM, Sithinamsuwan P, Allen IE, Chalermchai T, Tipsuk S, Phanuphak N, Jagodzinski L, Kim JH, Ananworanich J, Marovich MA, Valcour VG. Sex differences in soluble markers vary before and after the initiation of antiretroviral therapy in chronically HIV-infected individuals. AIDS. 2016 Jun 19;30(10):1533-42. doi: 10.1097/QAD.0000000000001096. PubMed PMID: 26990631; PubMed Central PMCID: PMC4889571.
Wieczorek L, Krebs SJ, Kalyanaraman V, Whitney S, Tovanabutra S, Moscoso CG, Sanders-Buell E, Williams C, Slike B, Molnar S, Dussupt V, Alam SM, Chenine AL, Tong T, Hill EL, Liao HX, Hoelscher M, Maboko L, Zolla-Pazner S, Haynes BF, Pensiero M, McCutchan F, Malek-Salehi S, Cheng RH, Robb ML, VanCott T, Michael NL, Marovich MA, Alving CR, Matyas GR, Rao M, Polonis VR. Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research. J Virol. 2015 Aug;89(15):7478-93. doi: 10.1128/JVI.00412-15. Epub 2015 May 13. PubMed PMID: 25972551; PubMed Central PMCID: PMC4505676.