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SELECTED PUBLICATIONS

Maynard lab members underlined; complete Google Scholar listing here.

►  Qerqez AN*, Silva RP* and Maynard JA. Outsmarting pathogens with antibody engineering. Annual Review of Chem & Biochem Eng, 14: 217-241, (2023). [link]

►  Silva R,* Huang Y*, Nguyen AW*, Hsieh C-L, Olaluwoye OS, Kaoud TS, Wilen RE, Qerqez AN,

Park JG, Khalil AM, Azouz LR, Le KC, Bohanon AL, DiVenere AM, Liu Y, Lee AG, Amengor D,

Shoemaker SR, Costello SM, Padlan EA, Marqusee S, Martinez-Sobrido L, Dalby K, D’Arcy S,

McLellan JS, Maynard JA. Identification of a conserved S2 epitope present on spike

proteins from all highly pathogenic coronaviruses. Elife, 12:e83710 (2023), [bioRxiv][link]

      UT News commentary, KUT News

 

►  Bowen JE, Park Y-J, Stewart C, Brown JT, Sharkey WK, Walls AC, Joshi A, Sprouse KR, McCallum M, Tortorici MA, Franko NM, Logue JK, Mazzitelli IG, Nguyen AW, Silva RP, Huang Y, Low JS, Jerak J, Tiles SW, Ahmed K, Shariq A, Dan JM, Zhang Z, Weiskopf D, Sette A, Snell G, Posaved CM, Talat Iqbal N, Geffner J, Bandera A, Gori A, Sallusto F, Maynard JA, Crotty S, Van Voorhis W, Simmerling C, Grifantini R, Chu HY, Corti D, Veesler D. SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines. Science Immunology eadf1421 (2022). [link]

 

►  Liu, Y, Nguyen AW* and Maynard JA*. Engineering antibodies for conditional activity in the solid tumor microenvironment.  Curr Opin Biotechnol, invited review, 78: 102809 (2022). [link]

►  DiVenere AM*, Amengor DA*, Silva RP, Goldsmith JA, McLellan JS and Maynard JA. Blockade of the adenylate cyclase toxin synergizes with opsonizing antibodies to protect mice against B. pertussismBio, e01527-22 (2022). [link]

                                                                           ►  Goldsmith J, DiVenere AM, Maynard JA, McLellan JS. Structural basis for non-canonical                                                                                  integrin engagement by the Bordetella adenylate cyclase toxin. Cell Reports, 40(7):                                                                                            111196 (2022). [link]

 

 

►  Liu Y, Lee AG, Nguyen AW and Maynard JA. An antibody Fc engineered for

conditional ADCC at the low tumor microenvironment pH. JBC, 298(4): 101798

(2022). [link] 

 

►  Silva RP, DiVenere AM, Amengor D, Maynard JA. Antibodies binding diverse pertactin

epitopes protect mice from B. pertussis. JBC, 298(3): 101715 (2022). [link]

 

 

 

                                                                                  ►  Costello SM, Shoemaker SR, Hobbs HT, Nguyen AW, Hsieh C-L, Maynard JA, McLellan JS,                                                                                         Pak JE,  Marqusee S. The SARS-CoV-2 spike reversibly samples an open-trimer conformation                                                                                         exposing novel epitopes. Nature Structural & Molecular Biology 29: 229-238 (2022). [link]

 

►  Goldsmith J, DiVenere AM, Maynard JA, McLellan JS. Structural basis for

antibody binding to adenylate cyclase toxin reveals RTX-linkers as key

neutralization-sensitive epitopes. Plos Pathogens 17(9): e1009920 (2021). [link]

                                                                            ►  Patterson-Orazem AC*, Qerqez AN*, Azouz LR*, Thu Ma M*, Hill SE, Ku Y, Schildmeyer LA,                                                                                           Maynard JA and Lieberman RL. Recombinant antibodies targeting the leucine zipper of misfolding-                                                                             prone myocilin: towards a toolbox of conformation-dependent reagents. JBC 297(3): 101067. (2021)                                                                               [link]

►    Nguyen AW and Maynard JA. Engineering antibody-based therapeutics: progress and opportunities. Invited review in Protein Engineering: Tools and Applications, edited by Huimin Zhao, Sang Yup Lee, Jens Nielsen, Gregory Stephanopoulos (2021). [link]

►   Hsieh C-L, Goldsmith JA, Schaub JM, DiVenere AM, Kuo H-C, Javanmardi K, Le KC, Wrapp D,

Lee AG, Liu Y, Chou C-W, Byrne PO, Hjorth CK, Johnson NV, Ludes-Meyers J, Nguyen AW, Park J,

Wang N, Amengor D, Maynard JA*, Finkelstein IJ*, McLellan JS. Structure-based design of

prefusion-stabilized SARS-CoV-2 spikes. Science, eabd0826. doi: 10.1126/science.abd0826.

(2020)  [link]

►   Tanno H, McDaniel JR, Stevens CA, Voss WN, Durrett R, Lee J, Gollihar J, Tanno Y, Delidakis G, Pothukuchy A, Ellefson JW, Goronzy JJ, Maynard JA, Ellington AE, Ippolito GC, Georgiou G. A Facile technology for the high throughput sequencing of the paired VH:VL and TCRb:TCRa repertoires. Science Advances 6(17): eaay9093 (2020). DOI: 10.1126/sciadv.aay9093. [link]

►   Nguyen AW, DiVenere AM, Papin JA, Connelly S, Kaleko M and Maynard JA, Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons. Science Advances 6 (6): eaay9258 (2020). DOI: 10.1126/sciadv.aay9258 [link]

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In this paper, we tested a specific approach to disease prevention that could be readily translated to humans. Pertussis continues to kill ~160,000 kids annually, primarily in resource limited areas. In these areas, if a child is going to see a clinician, this will most likely to happen at birth, when they are too young to be vaccinated against pertussis or any of the other major childhood diseases. However, these children could be given an at-birth injection of purified antibodies to provide “instant immunity” to prevent disease. If engineered to remain active in the body for an extended period of time, these antibodies could protect infants for their first 4 months of life. After this critical newborn period, infants could become infected and sick, but their more mature immune systems greatly reduce the risk of severe disease, long term effects and death.

 

With our collaborators, we evaluated the potential for at-birth antibody prophylaxis to prevent the symptoms of pertussis infection in newborn baboons, who exhibit similar responses to infection as human infants. The day after birth, baboons were given an antibody engineered to block the effects of pertussis toxin, then infected with pertussis five weeks later. Animals who were infected became very ill while those receiving antibody were clinically normal in terms of survival, coughing and other measures of disease. 

 

This advance is exciting not just as a strategy to prevent pertussis but because the data support the use of antibody prophylaxis more generally to prevent specific infections in high-risk populations.

TCR_Fc_cartoon.jpg

►   Wagner EK*, Qerqez AN*, Stevens CA, Nguyen AW, Delidakis G and Maynard JA. Human cytomegalovirus-specific T cell receptor engineered for high affinity and soluble expression using mammalian cell display. J Biological Chemistry, 294: 5790 (2019)  [link]

  • Editor's pick - top 2% of papers published in JBC, press release [link]

  • Author profiles: Ellen Wagner and Ahlam Qerqez

  • Related commentary, "Weaponizing T cell receptors through molecular engineering" [link]

  • Included in JBC's special 2020 issue highlighting contributions by women scientists to commemorate the ratification of the 19th Amendment and women's right to vote. [link]

In this paper, we engineered T cell receptors (TCR), which are normally present only on the surface of T cells and bind intracellular peptides presented on the surface of a target cell, for expression as a soluble protein with an antibody Fc domain and to bind the target peptide with antibody-like nanomolar affinity. A key innovation was the use of our mammalian cell display platform for TCR engineering since TCRs are recalcitrant to expression in bacteria and yeast. Using this approach, we hope to expand the range of proteins that can be targeted by therapeutic proteins to include intracellular proteins which are not accessible to antibodies and to develop novel therapeutics able to specifically target virally infected cells. 

►    Wagner EK and Maynard JA. Engineering therapeutic antibodies to combat infectious diseases, Current Opinion in Chemical Engineering19: 131-141 (2018). [link]

►    Entzminger KC*, Hyun JM*, Pantazes RJ*, Patterson-Orazem AC, Qerqez AN, Frye ZP, Hughes RA, Ellington AD, Lieberman RL, Maranas CD, Maynard JA. De novo design of antibody complementarity determining regions binding a FLAG tetra-peptide. Scientific Reports 7: 10295 (2017). [link]

 

 

►    Wagner EK, Wang X, Bui A, Maynard JA. Synergistic neutralization of pertussis toxin by a bispecific antibody in vitro and in vivo. Clinical & Vaccine Immunology, 23 (11): 851-862 (2016). [link]

►    Nguyen AW*, Wagner EK*, Laber JR, Goodfield L, Smallridge WE, Harvill ET, Papin JF, Wolf RF, Padlan EA, Bristol A, Kaleko M, Maynard JA. A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough. Science Translational Medicine 7 (316): 316ra195 (2015). [link]

►    Kowalsky CA, Faber MS, Nath A, Dann HE, Kelly VW, Liu L, Shanker P, Wagner EK, Maynard JA, Chan C, and Whitehead TA*. Rapid fine conformational epitope mapping using comprehensive mutagenesis and deep sequencing. J Biological Chemistry 290 (44): 26457-70 (2015). [link]

►    Wang X, Gray MC, Hewlett EL  and Maynard JA*.  The Bordetella adenylate cyclase Toxin RTX domain is immunodominant and elicits neutralizing antibodies. The Journal of Biological Chemistry  290(6): 3576-91 (2015). [link]

►   Entzminger KC, Johnson JL, Hyun J, Lieberman RL, and Maynard JA. Increased Fab thermoresistance via VH-targeted directed evolution. Special antibody issue: Protein Engineering, Design & Selection 28(10): 365-77 (2015). [link]

►     Wang X, Coljee VW and Maynard JA*.  Back to the future: recombinant polyclonal antibody therapeutics.  Current Opinion in Chemical Engineering 2 (4): 405-415 (2013).  Invited review. [link]

►    Johnston KP*, Maynard JA*, Truskett, TM*, Miller MA, Borwankar A, Wilson BK, Khan TA and Kaczorowski KJ. Stable, self-crowded protein nanoclusters. ACS Nano, 6(2): 1357-69 (2012). [link]

 

►    Sutherland JN and Maynard JA*. Characterization of a key neutralizing epitope on pertussis toxin recognized by the monoclonal antibody 1B7, Biochemistry, 48: 11982-11993 (2009). [link]

Undergraduate, graduate and post-doctoral work

►    Leysath CE, Monzingo AF, Maynard JA, Barnett J, Georgiou G, Iverson BL, and Robertus JD. Crystal structure of the engineered neutralizing antibody M18 complexed to the anthrax protective antigen. J Molecular Biology 387 (3): 680-693 (2009). [link]

►    Feng D, Bond, C, Ely, L, Maynard, J and Garcia, KC.  Structural evidence of a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon.' Nature Immunology, 8 (9): 975-983 (2007). [link]

►    Maynard JA, Adams EJ, Krogsgaard M, Petersson K, Liu C and Garcia KC.  High-level bacterial secretion of single-chain alpha-beta T cell receptors. Journal of Immunological Methods 306: 51-67 (2005). [link]


►    Maynard J, Petersson KP, Wilson DH, Adams EJ, Blondelle SJ, Boulanger MJ, Wilson DB, and Garcia KC. Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity. Immunity, 22: 81-92 (2005). [link]
 

►    Maynard JA, Braat-Maassen K, Leppla SH, Brasky K, Patterson J, Iverson BL, and Georgiou G.  Protection to anthrax toxin correlates with recombinant antibody affinity.   Nature Biotechnology, 20 (6): 597-602 (2002). [link]
•    Commentary in Science 297:201-202 (2002), Science News 154:157  (1998).

•    Developed by Elusys; FDA approved for human use as Anthim (Obiltoxaximab) in March 2016


►    Mao Y, Chen J, Maynard J, Zhang B, and Quiocho F.  A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.  Cell 104: 433-440 (2001). [link]


►    Maynard JA, and Georgiou G.  Antibody engineering.  Annual Review of Biomedical Engineering, 2: 339-376 (2000). [link]
 

►    Yee D, Maynard J, and Wood TK.  Rhizoremediation of trichloroethylene by a recombinant, root-colonizing Pseudomonas fluorescens strain expressing toluene ortho-Monooxygenase constitutively.  Applied and Environmental Microbiology, 64 (1): 112-118 (1998). [link]

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