Contact

  • Academic
    phamd@stanford.edu
    University - Student Department: BioPhysics Position: Graduate

All Publications

  • A broad antibody with enhanced HIV-1 neutralization via bispecific antibody-mediated prepositioning. Nature communications Kim, S., Radford, C. E., Xu, D., Zhong, J., Do, J., Pham, D. M., Travisano, K. A., Filsinger Interrante, M. V., Bruun, T. U., Rezek, V., Wilder, B., Palomares, M., Seaman, M. S., Kitchen, S. G., Bloom, J. D., Kim, P. S. 2025; 16 (1): 4617

    Abstract

    Antibodies targeting the highly conserved prehairpin intermediate (PHI) of class I viral membrane-fusion proteins are generally weakly neutralizing and are not considered viable therapeutic agents. We previously demonstrated that antibodies targeting the gp41 N-heptad repeat (NHR), which is transiently exposed in the HIV-1 PHI, exhibit enhanced broad neutralization in cells expressing the Fc receptor, FcγRI. To enhance neutralization in cells lacking FcγRI, we here develop a bispecific antibody (bsAb) by fusing an NHR-targeting antibody to an antibody against CD4, the HIV-1 receptor on T cells. The bsAb provides a 5000-fold neutralization enhancement and shows unprecedented neutralization breadth compared to existing broadly neutralizing antibodies. Importantly, the bsAb reduces viral load in HIV-1-infected humanized male mice, and viral envelope sequencing under bsAb pressure revealed an NHR mutation that potentially impairs viral fitness. These findings validate the NHR as a potential HIV-1 therapeutic target, setting the stage for a new class of broadly neutralizing antibodies.

    View details for DOI 10.1038/s41467-025-60035-6

    View details for PubMedID 40383778

    View details for PubMedCentralID 2517140