Xia Xie

All Publications

• Mucosal vaccination in mice provides protection from diverse respiratory threats. Science (New York, N.Y.) Zhang, H., Floyd, K., Fang, Z., Hoffmann, F. A., Lee, A., Froggatt, H. M., Bharj, G., Xie, X., Eppler, H. B., Santagata, J. M., Wang, Y., Hu, M., Fox, C. B., Arunachalam, P. S., Baric, R., Suthar, M. S., Pulendran, B. 2026: eaea1260

  Abstract

  Traditional vaccines target specific pathogens, limiting their scope against diverse respiratory threats. We describe an intranasal liposomal formulation combining toll-like receptor (TLR) 4 and 7/8 ligands with a model antigen, ovalbumin, that provided broad, durable protection in mice for at least 3 months against infection with SARS-CoV-2 and Staphylococcus aureus. In addition, the vaccine protected mice from other viruses (SARS-CoV-2, SARS, SCH014 coronavirus), bacteria (Acinetobacter baumannii), and allergens. Protection was mediated by persistent ovalbumin-specific CD4+ and CD8+ memory T cells that imprinted alveolar macrophages (AMs), enhancing antigen presentation and antiviral immunity. Following infection, vaccinated mice mounted rapid pathogen-specific T cell and antibody responses and formed ectopic lymphoid structures in the lung. These results reveal a class of "universal vaccines" against diverse respiratory threats.

  View details for DOI 10.1126/science.aea1260

  View details for PubMedID 41712698

• Antibiotic-induced gut microbiome perturbation alters the immune responses to the rabies vaccine. Cell host & microbe Feng, Y., de Jong, S. E., Oliveira, A. P., Samaha, H., Yang, F., Hu, M., Wang, Y., Beydoun, N., Xie, X., Zhang, H., Kazmin, D., Fang, Z., Zou, J., Gewirtz, A. T., Boyd, S. D., Hagan, T., Rouphael, N., Pulendran, B. 2025

  Abstract

  The gut microbiome plays a crucial role in modulating human immunity. Previously, we reported that antibiotic-induced microbiome perturbation affects influenza vaccine responses, depending on pre-existing immunity levels. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on both primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration reduced the gut bacterial load, with a long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced (1) an enhanced pro-inflammatory signature early after vaccination, (2) a shift in the balance of vaccine-specific T-helper 1 (Th1) to T-follicular-helper response toward Th1 phenotype, and (3) profound alterations in metabolites, particularly in secondary bile acids in the blood. By integrating multi-omics datasets, we generated a multiscale, multi-response network that revealed key regulatory nodes, including the microbiota, secondary bile acids, and humoral immunity to vaccination.

  View details for DOI 10.1016/j.chom.2025.03.015

  View details for PubMedID 40252648

• System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans. Nature immunology Cortese, M., Hagan, T., Rouphael, N., Wu, S. Y., Xie, X., Kazmin, D., Wimmers, F., Gupta, S., van der Most, R., Coccia, M., Aranuchalam, P. S., Nakaya, H. I., Wang, Y., Coyle, E., Horiuchi, S., Wu, H., Bower, M., Mehta, A., Gunthel, C., Bosinger, S. E., Kotliarov, Y., Cheung, F., Schwartzberg, P. L., Germain, R. N., Tsang, J., Li, S., Albrecht, R., Ueno, H., Subramaniam, S., Mulligan, M. J., Khurana, S., Golding, H., Pulendran, B. 2025; 26 (1): 116-130

  Abstract

  We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity. We found that TPO administration enhanced the durability of vaccine-induced antibody responses. TPO-activated megakaryocytes also promoted survival of human bone-marrow plasma cells through integrin β1/β2-mediated cell-cell interactions, along with survival factors APRIL and the MIF-CD74 axis. Using machine learning, we developed a classifier based on this platelet-associated signature, which predicted antibody response longevity across six vaccines from seven independent trials, highlighting a conserved mechanism for vaccine durability.

  View details for DOI 10.1038/s41590-024-02036-z

  View details for PubMedID 39747435

  View details for PubMedCentralID 9085459

• A comparative immunological assessment of multiple clinical-stage adjuvants for the R21 malaria vaccine in nonhuman primates. Science translational medicine Arunachalam, P. S., Ha, N., Dennison, S. M., Spreng, R. L., Seaton, K. E., Xiao, P., Feng, Y., Zarnitsyna, V. I., Kazmin, D., Hu, M., Santagata, J. M., Xie, X., Rogers, K., Shirreff, L. M., Chottin, C., Spencer, A. J., Dutta, S., Prieto, K., Julien, J. P., Tomai, M., Fox, C. B., Villinger, F., Hill, A. V., Tomaras, G. D., Pulendran, B. 2024; 16 (758): eadn6605

  Abstract

  Authorization of the Matrix-M (MM)-adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization for malaria prevention in children are a milestone in the fight against malaria. Yet, our understanding of the innate and adaptive immune responses elicited by this vaccine remains limited. Here, we compared three clinically relevant adjuvants [3M-052 + aluminum hydroxide (Alum) (3M), a TLR7/8 agonist formulated in Alum; GLA-LSQ, a TLR4 agonist formulated in liposomes with QS-21; and MM, the now-approved adjuvant for R21] for their capacity to induce durable immune responses to R21 in macaques. R21 adjuvanted with 3M on a 0, 8, and 23-week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/MM vaccine administered using a 0-4-8-week regimen and persisted up to 72 weeks with a half-life of 337 days. A booster dose at 72 weeks induced a recall response similar to the R21/MM vaccination. In contrast, R21/GLA-LSQ immunization induced a lower, short-lived response at the dose used. Consistent with the durable serum antibody responses, MM and 3M induced long-lived plasma cells in the bone marrow and other tissues, including the spleen. Furthermore, whereas 3M stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, MM induced enhanced expression of interferon- and TH2-related signatures more highly after the booster vaccination. Collectively, these findings provide a resource on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M as another adjuvant for malarial vaccines.

  View details for DOI 10.1126/scitranslmed.adn6605

  View details for PubMedID 39083589