Sheena Vasquez

All Publications

• Identifying key interactions of monoclonal antibodies that target the HuCoV-HKU1 spike using cryo-EM Vasquez, S., Wang, L., Joseph, J., Wrapp, D., Eso, M. R., Kong, W., Corbett-Helaire, K. S., Barnes, C. O. CELL PRESS. 2026

  View details for Web of Science ID 001717804800147

• Oriented Multivalent Display Drives Consistent Serum Immunodominance to the Ebola Virus Glycoprotein. ACS central science Zheng, C., Rubio, A. A., Vasquez, S., Pham, D., Pan, Z., Barnes, C. O., Kim, P. S. 2026; 12 (1): 100-110

  Abstract

  Despite the vast diversity of B cell repertoires, serum antibody responses during viral infection often focus on a limited set of epitopesa phenomenon known as immunodominance. This inherent bias establishes a hierarchy of epitope responses, which often facilitates viral immune evasion and presents a major challenge for universal vaccine design. It remains unclear whether serum immunodominance is primarily driven by antigen-intrinsic properties or by the spatial constraints imposed by virion-bound antigen presentation. Here, using Ebola virus glycoprotein (GP) as a model system, we found that trimeric GP elicited varied epitope hierarchies between individual animals during primary immunization. In contrast, multivalent GP presentation on either a vesicular stomatitis virus or ferritin nanoparticlesin the native orientation found on the Ebola viruselicited highly consistent and more refined epitope hierarchies across multiple mice and guinea pigs. These findings reveal a key role of oriented multivalent presentation in shaping serum immunodominance. The striking consistency of epitope hierarchy among individuals suggests that oriented multivalent presentation may promote more uniform immune protection at the population level, beyond increasing the magnitude of antibody binding and neutralizing responses.

  View details for DOI 10.1021/acscentsci.5c01886

  View details for PubMedID 41625225

  View details for PubMedCentralID PMC12856675

• Oriented Multivalent Display Drives Consistent Serum Immunodominance to the Ebola Virus Glycoprotein ACS CENTRAL SCIENCE Zheng, C., Rubio, A. A., Vasquez, S., Pham, D., Pan, Z., Barnes, C. O., Kim, P. S. 2026

  View details for DOI 10.1021/acscentsci.5c01886

  View details for Web of Science ID 001659224400001

• Human Coronavirus HKU1 Neutralizing Monoclonal Antibodies Target Diverse Epitopes Within and Around the TMPRSS2 Receptor Binding Site. bioRxiv : the preprint server for biology Wang, L., Joseph, J., Vasquez, S., Wrapp, D., Sheahan, T. P., Dzuvor, C. K., Rosen, O., Kirchdoerfer, R. N., Abiona, O. M., Hammond, C., Shi, W., Moak, S. P., Kong, W. P., Zhang, Y., Eso, M. R., Brown, A. J., Ward, A. B., Baric, R., McLellan, J. S., Pierson, T. C., Mascola, J., Graham, B. S., Yassine, H. M., Barnes, C. O., Corbett-Helaire, K. S. 2025

  Abstract

  Endemic human coronaviruses (HCoVs), like HCoV-HKU1, account for ~30% of common cold/year and can cause serious upper and lower respiratory infections, yet no licensed vaccines target HCoVs. In fact, little is known about HCoV-HKU1's antigenic landscape. Thus, we characterized key interactions between HCoV-HKU1 spike (S) with monoclonal antibodies (mAbs) isolated from pre-pandemic HCoV-HKU1 convalescent PBMCs. We isolated 14 mAbs, which bound distinct S regions: receptor binding domain (RBD), N-terminal domain (NTD), and S2 subunit. Structural and functional studies revealed three groups of RBD-specific mAbs targeting diverse footprints within and around the TMPRSS2 receptor binding site, exemplified by: (1) The most potently neutralizing mAb, H501-022 (IC50 = 0.01 μg/mL), which recognizes the TMPRSS2 binding motif, thereby blocking receptor engagement; (2) mAb H501-008 (IC50 = 0.05 μg/mL) that binds a conserved, cross-reactive epitope outside of the TMPRSS2 binding site that is shared with HCoV-OC43; and (3) H501-018 (IC50 = 0.28 μg/mL) that recognizes both "up" and "down" RBD conformations at a distinct, non-overlapping site outside of the TMPRSS2 binding motif, distinguishing itself from H501-022 and H501-008, which bind exclusively to the "up" RBD conformation. These mAbs represent the first type-specific HCoV-HKU1 mAbs isolated from a convalescent donor. Our findings provide molecular insight into HCoV-HKU1 antibody recognition and neutralization mechanisms, importantly highlighting antigenic differences comparing HCoVs and pandemic CoVs - a critical step towards advancing universal CoV vaccine design.

  View details for DOI 10.1101/2025.10.29.685445

  View details for PubMedID 41279056

  View details for PubMedCentralID PMC12636560

• Structural investigations of the cytosolic iron-sulfur cluster assembly pathway late acting proteins Vasquez, S., Marquez, M. M., Buzuk, A., Drennan, C. L., Perlstein, D. L. CELL PRESS. 2024: 446A

  View details for Web of Science ID 001194120702567

• Structural and biochemical investigations of a HEAT-repeat protein involved in the cytosolic iron-sulfur cluster assembly pathway COMMUNICATIONS BIOLOGY Vasquez, S., Marquez, M. D., Brignole, E. J., Vo, A., Kong, S., Park, C., Perlstein, D. L., Drennan, C. L. 2023; 6 (1): 1276

  Abstract

  Iron-sulfur clusters are essential for life and defects in their biosynthesis lead to human diseases. The mechanism of cluster assembly and delivery to cytosolic and nuclear client proteins via the cytosolic iron-sulfur cluster assembly (CIA) pathway is not well understood. Here we report cryo-EM structures of the HEAT-repeat protein Met18 from Saccharomyces cerevisiae, a key component of the CIA targeting complex (CTC) that identifies cytosolic and nuclear client proteins and delivers a mature iron-sulfur cluster. We find that in the absence of other CTC proteins, Met18 adopts tetrameric and hexameric states. Using mass photometry and negative stain EM, we show that upon the addition of Cia2, these higher order oligomeric states of Met18 disassemble. We also use pulldown assays to identify residues of critical importance for Cia2 binding and recognition of the Leu1 client, many of which are buried when Met18 oligomerizes. Our structures show conformations of Met18 that have not been previously observed in any Met18 homolog, lending support to the idea that a highly flexible Met18 may be key to how the CTC is able to deliver iron-sulfur clusters to client proteins of various sizes and shapes, i.e. Met18 conforms to the dimensions needed.

  View details for DOI 10.1038/s42003-023-05579-3

  View details for Web of Science ID 001127256700003

  View details for PubMedID 38110506

  View details for PubMedCentralID PMC10728100