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Shelly Krebs, Ph.D.

Chief, B cell Biology Core

Dr. Shelly Krebs received her Ph.D. from Dartmouth Medical School in 2008 in 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 under Dr. Chip Sheppard, focusing on low-cost diagnostics and the development of a whole-inactivated HIV vaccine.

With continued interests in HIV vaccination, she performed a second postdoctoral fellowship with Dr. Nancy Haigwood 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 and immune activation in HIV infection and vaccination.

Research

A major challenge for HIV vaccine design has been to identify immunogens capable of eliciting strong, persistent immunity that is effective against a broad range of isolates. The results of RV144 painted a clearer picture as to the types of responses needed, and found that antibodies played a major role in efficacy. However, understanding the pathways to eliciting protective HIV antibody responses remains elusive.

A major goal of the Krebs laboratory is to further understand how HIV infected individuals naturally develop potent antibody responses to be able exploit these characteristics in the design of HIV immunogens. Her laboratory utilizes cutting edge technologies such as high throughput robotic assays to assess longitudinal B cell responses in infection and vaccination.

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.

Lab Members

Selected Publications

1. 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; RV397 Study Group.“Safety and efficacy of VRC01 broadly neutralizing antibodies in adults with acutely treated HIV (RV397): a phase 2, randomized, double-blind, placebo-controlled trial.” Lancet HIV. 2019 Apr 15.

2. Krebs SJ, Kwon YD, Schramm CA, Law WH, Donofrio G, Zhou KH, Gift S, Dussupt V, Georgiev IS, Schätzle S, McDaniel JR, Lai Y, Sastry M, Zhang B, Jarosinski M, Ransier A, Chenine AL, Asokan M, Bailer RT, Bose M, Cagigi A, Cale EM, Chuang G, 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 C, Shiakolas AR, Stephens T, Tsybovsky Y, Tucker C, Veradi R, Wang K, Zhou J, Zhou T, Georgiou G, Alam SM, Haynes BF, Rolland M, Matyas GR, Polonis VR, McDermott A, Douek DC, Shapiro L, Tovanabutra S , Michael NL, MascolaJR, Robb ML, Kwong PD, Doria-Rose NA., “Initiation and Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1 Infected Individual” Immunity 2019 Mar 19;50(3):677-691.e13.

3. Hellmuth, J., Slike BM, Sacdalan C, BestJ, Kroon E, Phanuphak N, Fletcher JLK, Prueksakaew P, JagodzinskiLL, Valcour V, Robb M, Ananworanich J, Allen IE, Krebs SJ, Spudich S on behalf of the SEARCH 010/RV254 and SEARCH013/RV304 Study Groups. “Very early ART initiation during acute HIV infection is associated with normalization of cerebrospinal fluid but not plasma markers of immune activation.” J Infect Dis. 2019 Jan 21

4. 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” In review JCI Insight, JCI Insight. 2018 May 17;3(10).

5. Krebs, S.J. and Ananworanich, J., “Immune activation during acute HIV infection and the impact of early antiretroviral therapy”, Curr Opin HIV AIDS. 2015 Nov 21. [Epub ahead of print]

6. Prentice HA, Tomaras GD, Geraghty DE, Apps R, Fong Y, Ehrenberg PK, Rolland M, Kijak GH, Krebs SJ, Nelson W, DeCamp A, Shen X, Yates NL, Zolla-Pazner S, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Ferrari G, McElrath MJ, Montefiori DC, Bailer RT, Koup RA, O'Connell RJ, Robb ML, Michael NL, Gilbert PB, Kim JH, Thomas R. “HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition”. Sci Transl Med. 2015 Jul 15;7(296):296ra112.

7.  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”; Journal of Virology. 2015 Aug 1;89(15):7478-93.

8.  Krebs, S.J., S. McBurney, D.N. Kovarik, C. Smith, J.P. Jaworski, W.F. Sutton, M. Trovato, G. Waagmeester, S.J. Barnett, P. DeBerardinis, and N.L. Haigwood, “Multimeric scaffolds displaying the HIV-1 Envelope MPER induce MPER-specific neutralizing antibodies when co-immunized with gp160 DNA vaccines”, PLOS One, 2014 Dec 16;9(12):e113463

9. Juan Pablo Jaworski, S. J. Krebs, M. Trovato, D.L. Kovarik, Z. Brower, W.F. Sutton, G. Waagmeester, R. Sartorius, L. D’Apice, N.A. Doria-Rose, D. Malherbe, D. Montefiori, S. Barnett, P. De Berardinis, and N. L. Haigwood, “Co-immunization With Mulitmeric Scaffolds and DNA Rapidly Induces Potent Autologous HIV-1 Neutralizing Antibodies and CD8+ T Cells”, PLOS One 2012; 7(2):e31464.