Publications
-
Title & Authors Journal Publication Date

Isolation of genetically diverse influenza antibodies highlights the role of IG germline gene variation and informs the design of population-comprehensive vaccine strategies.


Fischer AA, Corcoran M, Brouwer PJM, Chernyshev M, Gillespie RA, Nicoletto A, Loeffler JR, Ferguson JA, Rodriguez AJ, Narang S, van Gils MJ, Castro Dopico X, Kanekiyo M, Ward AB, Han J, Karlsson Hedestam GB.
bioRxiv July 7, 2025

A single residue change only differing by an atomic group can drive imprinting to influenza.


Sun J, Jo G, Troxell CA, Fu Y, Hoezl R, Lv H, Abozeid HH, Teo QW, Pholcharee T, McGrath JJC, Changrob S, Nelson SA, Yasuhara A, Huang M, Zheng NY, Chervin JC, Li L, Fernández-Quintero ML, Loeffler JR, Rodriguez AJ, Huang J, Swanson OM, Balmaseda A, Kuan G, Campredon L, Allen EK, Neumann G, Wu NC, Kawaoka Y, Krammer F, Thomas PG, Gordon A, Ward AB, Han J, Wilson PC.
Res Sq July 7, 2025

Vaccines combining slow release and follicle targeting of antigens increase germinal center B cell diversity and clonal expansion.


Rodrigues KA, Zhang YJ, Lam J, Aung A, Morgan DM, Romanov A, Maiorino L, Yousefpour P, Gibson G, Ozorowski G, Gregory JR, Amlashi P, Van R, Buckley M, Ward AB, Schief WR, Love JC, Irvine DJ.
Sci Transl Med June 18, 2025

Rapid acquisition of HIV-1 neutralization breadth in a rhesus V2 apex germline antibody mouse model after a single bolus immunization.


Ghosh AR, Habib R, Mishra N, Roark RS, Akauliya M, Albowaidey AA, Allen JD, Amereh K, Avillion G, Bottermann M, Liang B, Chaudhary N, Callaghan S, Dye J, Li X, Ellis-Pugh JR, Chowdhury RR, James NE, Liu X, Maiorino L, Maldonado P, Nedellec R, Oberoi P, Sowers KJ, Park Y, Prum T, Rodriguez L, Ssozi M, Torres J, Walsh AA, Warner JE, Weldon SR, Xu L, Wiehe K, Crispin M, Ward AB, Nair U, Hahn BH, Burton DR, Shapiro L, Kwong PD, Irvine DJ, Andrabi R, Shaw GM, Batista FD.
bioRxiv June 17, 2025

Virus glycoprotein nanodisc platform for vaccine design.


Rantalainen K, Liguori A, Ozorowski G, Flynn C, Steichen JM, Swanson O, Madden PJ, Baboo S, Phulera S, Gharpure A, Lu D, Kalyuzhniy O, Skog P, Terada S, Shil M, Diedrich JK, Georgeson E, Tingle R, Eskandarzadeh S, Lee WH, Alavi N, Goodwin D, Kubitz M, Amirzehni S, Himansu S, Sok D, Lee JH, Yates JR 3rd, Paulson JC, Crotty S, Schiffner T, Ward AB, Schief WR.
bioRxiv June 16, 2025

CD16a pairs form the basal molecular subunit for the NK-cell ADCC lytic synapse.


Ross P, Cid T, Fernández Quintero M, Loeffler J, Fatima H, Leaman DP, Matthias J, Spencer K, Zwick MB, Henderson SC, Ward AB, Mace EM, Murin CD.
J Immunol June 16, 2025

Antigenic and EM characterization of the Chiron experimental hepatitis C virus vaccine.


Hung SH, Torres JL, Chen F, Giang E, Ward AB, Law M.
Vaccine June 11, 2025

Germline-encoded recognition of peanut underlies development of convergent antibodies in humans.


Marini-Rapoport O, Andrieux L, Keswani T, Zong G, Duchen D, Yaari G, Min J, Lytle IR, Rosenberg AF, Fucile C, Kobie JJ, Piepenbrink MS, Sun T, Martin VM, Yuan Q, Shreffler WG, Seppo AE, Järvinen KM, Loeffler JR, Ward AB, Kleinstein SH, Pedersen LC, Fernández-Quintero ML, Mueller GA, Patil SU.
Sci Transl Med June 11, 2025

Vaccination of nonhuman primates elicits a broadly neutralizing antibody lineage targeting a quaternary epitope on the HIV-1 Env trimer.


Schleich FA, Bale S, Guenaga J, Ozorowski G, Àdori M, Lin X, Castro Dopico X, Wilson R, Chernyshev M, Cotgreave AT, Mandolesi M, Cluff J, Doyle ED, Sewall LM, Lee WH, Zhang S, O'Dell S, Healy BS, Lim D, Lewis VR, Ben-Akiva E, Irvine DJ, Doria-Rose NA, Corcoran M, Carnathan D, Silvestri G, Wilson IA, Ward AB, Karlsson Hedestam GB, Wyatt RT.
Immunity June 10, 2025

Microfluidics combined with electron microscopy for rapid and high-throughput mapping of antibody-viral glycoprotein complexes.


Sewall LM, de Paiva Froes Rocha R, Gibson G, Louie M, Xie Z, Bangaru S, Tran AS, Ozorowski G, Mohanty S, Beutler N, Rogers TF, Burton DR, Shaw AC, Batista FD, Chocarro Ruiz B, Torrents de la Peña A, Ward AB.
Nat Biomed Eng June 3, 2025

Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response.


Matsuda K, Harrison M, Wettstein E, Pederson J, Pullano AA, Bolkhovitinov L, Kim B, Steinberg I, Griesman T, Stuccio S, Rogan D, Patamawenu A, Shofner T, Wright NE, Webber JD, Van't Veer F, Roenicke R, Koory E, Roeder PM, Ober E, Leach B, Tsybovsky Y, Stephens T, Del Moral-Sanchez I, Bontjer I, McGinnes-Cullen LW, Chu E, Liang J, Torres JL, Lin RN, Tran AS, Dziubla G, Serebryannyy L, Narpala S, Lin B, Castro M, Ozorowski G, Ward AB, Sanders RW, Kwong PD, Guenaga J, Wyatt R, Morrison T, Connors M.
Nat Commun June 3, 2025

Local structural flexibility drives oligomorphism in computationally designed protein assemblies.


Khmelinskaia A, Bethel NP, Fatehi F, Mallik BB, Antanasijevic A, Borst AJ, Lai SH, Chim HY, Wang JY', Miranda MC, Watkins AM, Ogohara C, Caldwell S, Wu M, Heck AJR, Veesler D, Ward AB, Baker D, Twarock R, King NP.
Nat Struct Mol Biol June 1, 2025

Many naturally occurring protein assemblies have dynamic structures that allow them to perform specialized functions. Although computational methods for designing novel self-assembling proteins have advanced substantially over the past decade, they primarily focus on designing static structures. Here we characterize three distinct computationally designed protein assemblies that exhibit unanticipated structural diversity arising from flexibility in their subunits. Cryo-EM single-particle reconstructions and native mass spectrometry reveal two distinct architectures for two assemblies, while six cryo-EM reconstructions for the third likely represent a subset of its solution-phase structures. Structural modeling and molecular dynamics simulations indicate that constrained flexibility within the subunits of each assembly promotes a defined range of architectures rather than nonspecific aggregation. Redesigning the flexible region in one building block rescues the intended monomorphic assembly. These findings highlight structural flexibility as a powerful design principle, enabling exploration of new structural and functional spaces in protein assembly design.

Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope.


Bick MV, Puig E, Beauparlant D, Nedellec R, Burton I, Ardaghi K, Zalunardo TR, Bastidas R, Li X, Guenaga J, Lee WH, Wyatt R, Zhu W, Crispin M, Ozorowski G, Ward AB, Burton DR, Hangartner L.
Cell Rep April 22, 2025

Distinct oligomeric assemblies of STING induced by non-nucleotide agonists.


Gharpure A, Sulpizio A, Loeffler JR, Fernández-Quintero ML, Tran AS, Lairson LL, Ward AB.
Nat Commun April 11, 2025

STING plays essential roles coordinating innate immune responses to processes that range from pathogenic infection to genomic instability. Its adaptor function is activated by cyclic dinucleotide (CDN) secondary messengers originating from self (2'3'-cGAMP) or bacterial sources (3'3'-CDNs). Different classes of CDNs possess distinct binding modes, stabilizing STING's ligand-binding domain (LBD) in either a closed or open conformation. The closed conformation, induced by the endogenous ligand 2'3'-cGAMP, has been extensively studied using cryo-EM. However, significant questions remain regarding the structural basis of STING activation by open conformation-inducing ligands. Using cryo-EM, we investigate potential differences in conformational changes and oligomeric assemblies of STING for closed and open conformation-inducing synthetic agonists. While we observe a characteristic 180° rotation for both classes, the open-LBD inducing agonist diABZI-3 uniquely induces a quaternary structure reminiscent but distinct from the reported autoinhibited state of apo-STING. Additionally, we observe slower rates of activation for this ligand class in functional assays, which collectively suggests the existence of a potential additional regulatory mechanism for open conformation-inducing ligands that involves head-to-head interactions and restriction of curved oligomer formation. These observations have potential implications in the selection of an optimal class of STING agonist in the context of a defined therapeutic application.

Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins.


Guthmiller JJ, Yu-Ling Lan L, Li L, Fu Y, Nelson SA, Henry C, Stamper CT, Utset HA, Freyn AW, Han J, Stovicek O, Wang J, Zheng NY, Huang M, Dugan HL, Tepora ME, Zhu X, Chen YQ, Palm AE, Shaw DG, Loganathan M, Francis BF, Sun J, Chervin J, Troxell C, Meade P, Leung NHL, Valkenburg SA, Cobey S, Cowling BJ, Wilson IA, García-Sastre A, Nachbagauer R, Ward AB, Coughlan L, Krammer F, Wilson PC.
Immunity April 8, 2025

Ab initio prediction of specific phospholipid complexes and membrane association of HIV-1 MPER antibodies by multi-scale simulations.


Maillie CA, Golden K, Wilson IA, Ward AB, Mravic M.
Elife April 7, 2025

Deposition of complement regulators on the surface of Plasmodium falciparum merozoites depends on the immune status of the host.


Bassi MR, Cristinoi B, Buitenwerf F, Cuadrado MB, Björnsson KH, Walker MR, Partey FD, Ward AB, Ofori MF, Barfod L.
PLoS Pathog April 1, 2025