► 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, eaay9258 (2020). DOI: 10.1126/sciadv.aay9258 [link]
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 provide proof-of-concept that at-birth antibody prophylaxis could prevent many other serious illnesses affecting newborns.
► 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]
Related commentary, "Weaponizing T cell receptors through molecular engineering" [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.
► Nguyen AW and Maynard JA. Engineering Antibodies on the Surface of CHO cells. Invited Chapter in the Genotype-Phenotype Coupling issue in the Methods in Molecular Biology series; edited by Stefan Zielonka, Merck KgaA. Methods Molec Biol 2020;2070:397-422. [link]
► Nguyen AW and Maynard JA. Engineering antibody-based therapeutics: progress and opportunities. Invited review submitted for Protein Engineering: Tools and Applications, edited by Huimin Zhao. In press.
► Acquaye-Seedah E*, Huang Y*, Sutherland JN*, DiVenere AM and Maynard JA. Antibody-mediated neutralization of pertussis toxin by altered cellular trafficking. Cellular Microbiology, 20: e12948, (2018). [link]
► Boehm DT, Hall JM, Wong TY, DiVenere A, Sen-Kilic E, Bevere JR, Bradford SD, Blackwood CB, Elkins C, DeRoos KA, Gray MC, Cooper CG, Varney ME, Maynard JA, Hewlett EL, Barbier M, Damron FH. Evaluation of adenylate cyclase toxoid antigen in acellular pertussis vaccines using a Bordetella pertussis challenge model in mice. Infection & Immunity, 86(10): e00857-17. (2018). [link]
► Acquaye-Seedah EA, Reczek EE, Russell HH, DiVenere AM, Sandman SO, Collins JH, Stein CA, Whitehead TA and Maynard JA. Characterization of individual human antibodies binding pertussis toxin stimulated by acellular immunization. Infection & Immunity 86(6): e00004-18 (2018). [link]
► Nguyen AW, Le KC, Maynard JA. Identification of high affinity HER2 antibodies using CHO Fab surface display. Protein Engineering Design Selection, 31(3): 91-101 (2018). [link]
► Bradbury ARM, Trinklein ND, Thie H, Wilkinson IC, Tandon AK, Anderson S, Bladen CL, Jones S, Force Aldred S, Bestagno M, Burrone O, Maynard JA, Ferrara F, Trimmer JS, Görnemann J, Glanville J, Wolf P, Frenzel A, Wong J, Yu X, Eng H-Y, Lane D, Lefranc M-P, Clark M, & Dübel S. When monoclonal antibodies are not monospecific: hybridomas frequently express additional functional variable regions. mAbs, 10(4):539-546 (2018). [link]
► Ha Y, Ko S, Kim I, Huang Y, Mohanty K, Huh C, Maynard JA. Recent advances incorporating superparamagnetic nanoparticles into immunoassays. ACS Applied Nano Materials 1 (2): 512-521 (2018). [link]
► Maynard JA and Gerecht S. Biological engineering: Emerging strategies to understand and engineer the human immune system. Current Opinion in Chemical Engineering, 19: 1-3 (2018). Editorial overview of issue on immuno-engineering. [link]
► Wagner EK and Maynard JA. Engineering therapeutic antibodies to combat infectious diseases, Current Opinion in Chemical Engineering, 19: 131-141 (2018). [link]
► Laber JR, Dear BJ, Martins ML, Jackson DE, Gollihar JD, Ellington AD, Truskett TM, Johnston KP, Maynard JA. Charge shielding prevents aggregation of supercharged GFP variants at high concentration. Molecular Pharmaceutics 14 (10): 3269-3280 (2017). [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]
► Wang X, Stapleton JA, Klesmith JA, Helwett EL, Whitehead TA, Maynard JA. Fine epitope mapping of two antibodies neutralizing the adenylate cyclase toxin. Biochemistry 56 (9): 1324-1336 (2017). [link]
► Nguyen AW, Wagner EK, Posada L, Liu X, Papin JF, Wolf RF, Connelly S, Kaleko M, Maynard JA. Prior exposure to Bordetella species as an excusion criterion in the baboon model of pertussis. J Vet Med Sci, 79 (1): 60-64 (2017). [link]
► Khan TA*, Wang ZX* and Maynard JA. Inclusion of an RGD motif alters invasin-integrin binding specificity. Biochemistry 55 (14): 2078-90 (2016). [link]
► Ha Y, Wang X, Liljestrand, HE, Maynard JA, Katz LE*. Bioavailability of fullerene under environmentally relevant conditions: Effects of humic acid and fetal bovine serum on accumulation in lipid bilayers and cellular uptake. Environmental Science and Technology 50(13): 6717-27 (2016). [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]
UT Alumni magazine, the Alcade, March-April 2016,
► 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]
► Johnson J, Entzminger KC, Hyun J, Kalyoncu S, Heaner D, Morales I, Sheppard A, Gumbart J, Maynard JA and Lieberman RL. Structural and biophysical characterization of epitope-specific engineered Fab fragment and complexation with membrane proteins: implications for co-crystallization. Acta Crystallographica Section D, 71: 896-906 (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]
► Miller MA, Rodrigues MA, Glass MA, Singh SK*, Johnston KP* and Maynard JA*. Frozen-state storage stability of a monoclonal antibody: aggregation is impacted by freezing rate and solute distribution. J Pharm Sci 102 (4): 1194-208 (2013). [link]
► Borwankar A, Dinen AK, Laber JR, Twu A, Wilson BR, Miller MA, Vier D, Maynard JA, Truskett TM* and Johnston KP*. Tunable equilibrium nanocluster dispersion at high protein concentrations. Soft Matter 9: 1766-1771 (2013). [link]
► Roy BR, Zhukov DV and Maynard JA*. Flanking residues are central to DO11.10 T cell hybridoma stimulation by ovalbumin 323-339 peptide. PLoS ONE 7 (10): e47585 (2012). [link]
► Miller MA, Khan TA, Kaczorowski K, Wilson BK, Dinen A, Rodrigues M, Borwankar AU, Truskett TM*, Johnston KP* and Maynard JA*. Dispersions of antibody nanoparticles formed by mixtures of crowding molecules retain activity and in vivo bioavailability. J Pharm Sci 101: 3763-3778 (2012). [link]
► Entzminger KC, Chang C, Myhre RO, McCallum KC, Maynard JA*. The skp chaperone sequesters kinetically trapped intermediates of soluble periplasmic proteins to reduce aggregation. Biochemistry 51: 4822-4834 (2012). [link]
► Kalyoncu S, Hyun JH, Pai JC, Johnson JL, Entzminger KC, Jain A, Heaner D, Morales IA, Truskett TM, Maynard JA*, Lieberman RL.* Effects of protein engineering and rational mutagenesis on crystal lattice of single chain antibody fragments: implications for membrane protein crystallization chaperones. Proteins, 82 (9): 1884-1895 (2014). [link]
► Acquaye EA, Frye Z and Maynard JA*. Immunotherapeutic approaches to prevent CMV-mediated disease. Rino Rappuoli, JE Crowe and Diana Boraschi, ed. Antibodies for Infectious Diseases, ASM Press and ASM Microbiol Spectrum 2 (1): 1-12 (2014). Invited review chapter. [link]
► Panthani MG, Khan TA, Reid DK, Hellebusch DJ, Rasch M, Maynard JA* and Korgel BA*. In vivo whole animal fluorescence imaging of a microparticle-based oral vaccine containing (CuInSxSe2-x)/ ZnS core/ shell quantum dots. Nano Letters: 3 (9): 4294-8 (2013). [link]
► Im HS, Sutherland JN, Maynard JA* and Oh S-H*. Nanopore-enabled, low-cost SPR instruments for quantifying a broad range of antibody-ligand binding kinetics. Analytical Chemistry, 84(4): 1941-7 (2012). [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]
UT Alumni magazine, the Alcade, March-April 2012.
Highlighted in Chemical & Engineering News.
News & Views by Phil Ball in Nature Materials, 11:185 (2012).
News & Views in Nanomedicine, 7(2): 311-312 (2012).
► Pai JC, Entzminger KC and Maynard JA. Ligation-free construction of random gene mutagenesis libraries in E. coli. Analytical Biochemistry, 421: 640-648 (2012). [link]
► Lieberman RL, Culver JA, Entzminger KC, Pai JC and Maynard JA. Crystallization chaperone strategies for membrane proteins. Methods 55: 293-302 (2011).
• Invited review, special issue on membrane protein crystallization. [link]
► Sutherland JN, Chang C, Yoder SM, Rock MT, Maynard JA. Antibodies recognizing protective pertussis toxin epitopes are preferentially elicited by natural infection versus acellular immunization. Clinical and Vaccine Immunology, 18 (6): 954 (2011). [link]
► Pai JC, Culver JA, Drury JE, Motani RS, Lieberman RL* and Maynard JA* Conversion of scFv peptide-binding specificity for crystal chaperone development. Protein Engineering, Design and Selection, 24: 419-428 (2011). [link]
► Ramalingam KI, Tomshine J, Maynard JA and Kaznessis Y. Forward engineering of synthetic biological AND-gates. J Biochemical Engineering, 47: 38-47 (2009). [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]
► Maynard, JA*, Lindquist, N, Sutherland, JN, Warrington, AE, Rodriguez, M, and Oh, SH*. Surface plasmon resonance for high-throughput ligand screening of membrane-bound proteins. Biotechnology J, 4 (11): 1542-1558 (2009). [link]
• Invited review, special issue on biosensors; cover art of the issue.
► 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]
► Pai JC, Sutherland JN and Maynard, JA. Progress towards recombinant anti-infective antibodies. Recent patents in anti-infective drug discovery. 4 (1):1-17 (2009). [link]
► Sivasubramanian A., Maynard JA, and Gray JJ. Modeling the structure of mAb 14B7 bound to the anthrax protective antigen. Proteins: Structure, Function, Bioinformatics, 70 (1): 218-230 (2008). [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, Myhre R., and Roy B. Microarrays in infection and immunity. Current Opinion in Chemical Biology. 11 (3): 306-315 (2007). [link]
► Maynard JA, Adams EJ, Krogsgaard M, Petersson K, Liu C and Garcia KC. High-level bacterial secretion of ab 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
► Maynard JA, Chen G, Iverson BL, and Georgiou G. In vitro scanning saturation mutagenesis. Methods in Molecular Biology, 182: 149-163 (2002). [link]
► 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]