Research Description

Molecular characterization of antibody-antigen complexes to guide the design of next-generation vaccines and therapeutics

Dr. Julien’s laboratory characterizes the mode of action of antibodies at the molecular level to guide the design of next-generation vaccines and therapies. A major focus of his laboratory is to use integrative structural biology approaches and biophysical techniques to characterize antibody-antigen interactions. This knowledge is then applied to develop next-generation therapeutic molecules fit-for-purpose using protein engineering. Through this work, Dr. Julien’s laboratory is generating three-dimensional glimpses of antibody mechanisms of action, with already several examples of how this information can be translated into the development of vaccine candidates against malaria and HIV-1, and antibodies with improved biological and developability characteristics against cancer and autoimmune targets.

Publications

View all publications on PubMed

A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo.
Burn Aschner C, Muthuraman K, Kucharska I, Cui H, Prieto K, Nair MS, Wang M, Huang Y, Christie-Holmes N, Poon B, Lam J, Sultana A, Kozak R, Mubareka S, Rubinstein JL, Rujas E, Treanor B, Ho DD, Jetha A, Julien JP.
Sci Transl Med. 2023 May 24; 15(697): eadf45. doi: 10.1126/scitranslmed.adf4549.  Read

Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses.
Kassardjian A, Sun E, Sookhoo J, Muthuraman K, Frias Boligan K, Kucharska I, Rujas E, Jetha A, Branch DR, Babiuk S, Barber B, Julien JP.
Cell Rep. 2023 Apr 25; 42(4): 112391. doi: 10.1016/j.celrep.2023.112391.  Read

Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model.
Ludwig J, Scally SW, Costa G, Hoffmann S, Murugan R, Lossin J, Prieto K, Obraztcova A, Lobeto N, Franke-Fayard B, Janse CJ, Lebas C, Collin N, Binter S, Kellam P, Levashina EA, Wardemann H, Julien JP.
npj Vaccines. 2023 Apr 7; 8: 52. doi: 10.1038/s41541-023-00653-7.  Read

Identification of highly potent transmission-blocking human monoclonal antibodies to Plasmodium falciparum Pfs230 in naturally exposed individuals.
Ivanochko D, Fabra-García A, Teelen K, van de Vegte-Bolmer M, van Gemert GJ, Newton J, Semesi A, de Bruijni M, Bolscher J, Ramjith J, Szabat M, Vogt S, Kraft L, Duncan S, Lee SM, Kamya MR, Feeney ME, Jagannathan P, Greenhouse B, Sauerwein RW, King CR, MacGill RS, Bousema T, Jore MM, Julien JP.
Immunity. 2023 Feb 14; 56(2): 420-432.e7. doi:10.1016/j.immuni.2023.01.013.  Read

Engineering pan–HIV-1 neutralization potency through multispecific antibody avidity.
Rujas E, Cui H, Burnie J, Aschner CB, Zhao T, Insausti S, Muthuraman K, Semesi A, Ophel J, Nieva JL, Seaman MS, Guzzo C, Treanor B, Julien JP.
Proc. Natl. Acad. Sci. U.S.A. 2022 Jan 21; 119(4):e2112887119. doi:10.1073/pnas.2112887119.  Read

Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses.
McLeod B, Mabrouk MT, Miura K, Ravichandran R, Kephart S, Hailemariam S, Pham TP, Semesi A, Kucharska I, Kundu P, Huang WC, Johnson M, Blackstone A, Pettie D, Murphy M, Kraft JC, Leaf EM, Jiao Y, van de Vegte-Bolmer M, van Gemert GJ, Ramjith J, King CR, MacGill RS, Wu Y, Lee KK, Jore MM, King NP, Lovell JF, Julien JP.
Immunity. 2022 Sep 13; 55, 1-13. doi:10.1016/j.immuni.2022.07.015.  Read

Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers.
Rujas E, Kucharska I, Tan YZ, Benlekbir S, Cui H, Zhao T, Wasney GA, Budylowski P, Guvenc F, Newton JC, Sicard T, Semesi A, Muthuraman K, Nouanesengsy A, Aschner CB, Prieto K, Bueler SA, Youssef S, Liao-Chan S, Glanville J, Christie-Holmes N, Mubareka S, Gray-Owen SD, Rubinstein JL, Treanor B, Julien JP.
Nat Commun. 2021. 12:3661. doi: 10.1038/s41467-021-23825.  Read

Structural ordering of the Plasmodium berghei circumsporozoite protein repeats by inhibitory antibody 3D11.
Kucharska I, Thai E, Srivastava A, Rubinstein JL, Pomès R, Julien JP.
eLife. 2020. 9:e59018. doi:10.7554/eLife.59018.  Read

Structural characterization of the ICOS/ICOS-L immune complex reveals high molecular mimicry by therapeutic antibodies.
Rujas E, Cui H, Sicard T, Semesi A, Julien JP.
Nat Commun. 2020. 11:5066. doi: 10.1038/s41467-020-18828-4.  Read

Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins.
Lee H, Beilhartz GL, Kucharska I, Raman S, Cui H, Lam M, Rubinstein JL, Schramek D, Julien JP, Melnyk RA, Taipale M.
Cell. 2020. 182 (2): 345–356.e16. doi: 10.1016/j.cell.2020.06.005.  Read

Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25.
McLeod B, Miura K, Scally SW, Bosch A, Nguyen N, Shin H, Kim D, Volkmuth W, Rämisch S, Chichester JA, Streatfield S, Woods C, Schief WR, Emerling D, King CR, Julien JP.
Nat Commun. 2019. 10: 4328. doi: 10.1038/s41467-019-11980-6.  Read

Structure-guided design fine-tunes pharmacokinetics, tolerability, and antitumor profile of multispecific frizzled antibodies.
Raman S, Beilschmidt M, To M, Lin K, Lui F, Jmeian Y, Ng M, Fernandez M, Fu Y, Mascall K, Duque A, Wang X, Pan G, Angers S, Moffat J, Sidhu SS, Magram J, Sinclair AM, Fransson J, Julien JP.
Proc. Natl. Acad. Sci. U.S.A. 2019. 116(14): 6812-6817. doi: 10.1073/pnas.1817246116.  Read

Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope.
Imkeller K, Scally SW, Bosch A, Martí GP, Costa G, Triller G, Murugan R, Renna V, Jumaa H, Kremsner PG, Sim BKL, Hoffman SL, Mordmüller B, Levashina E, Julien JP, Wardemann H.
Science. 2018. 360(6395): 1358-1362. doi: 10.1126/science.aar5304.  Read

Molecular basis of human CD22 function and therapeutic targeting.
Ereño-Orbea J*, Sicard T*, Cui H, Mazhab-Jafari MT, Benlekbir S, Guarné A, Rubinstein JL, Julien JP.
Nat Commun. 2017 Oct 2; 8:764. doi: 10.1038/s41467-017-00836-6.  Read

Crystal structure of a soluble cleaved HIV-1 envelope trimer.
Julien JP, Cupo A, Sok D, Stanfield RL, Lyumkis D, Deller MC, Klasse PJ, Burton DR, Sanders RW, Moore JP, Ward AB, Wilson IA.
Science. 2013. 342(6165):1477-83. doi: 10.1126/science.1245625.  Read

Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer.
Lyumkis D, Julien JP, de Val N, Cupo A, Potter CS, Klasse PJ, Burton DR, Sanders RW, Moore JP, Carragher B, Wilson IA, Ward AB.
Science. 2013. 342(6165):1484-90. doi: 10.1126/science.1245627.  Read