Sandra Bos

Contributions to Public Health

• High-resolution serological tools to resolve flavivirus infection histories: I develop scalable serological platforms that resolve flavivirus infection histories at high resolution. These tools have notably uncovered the contribution of inapparent infections, enabled the first serotype-resolved epidemiology of primary dengue across the full disease spectrum, revealed silent circulation of serotypes missed entirely by symptomatic surveillance, and refined estimates of serotype-specific force of infection and virulence. Ongoing work addresses serodiagnostics for other flaviviruses. 
  • Bos S* & Zambrana JV*, Duarte EM, Graber AL, Huffaker J, Montenegro C, Lakshmanane P, Gordon A, Balmaseda A, and Harris E. Inapparent primary infections reveal hidden serotype-specific epidemiological patterns and spectrum of infection outcome: a cohort study in Nicaragua. Lancet Infectious Diseases. 2024. doi:10.1016/S1473-3099(24)00566-8.
• Non-reciprocal immune interactions between flaviviruses: Using human cohorts and non-human primate models, my work established that immune interactions among flaviviruses are structured, asymmetric, and order-dependent. Prior infection with one flavivirus can increase disease risk upon subsequent infection with a second, while the reverse sequence is protective (A protects against B, but B is a risk for A). Order also shapes the antibody response itself: A→B and B→A generate distinct antibody profiles, providing a mechanistic foundation for risk stratification and vaccine schedule design. 
  • Zambrana JV* & Hasund CM* & Aogo RA*, Bos S, Arguello S, Gonzalez K, Collado D, Miranda T, Kuan G, Gordon A, Balmaseda A, Katzelnick L, and Harris E. Primary exposure to Zika virus increases risk of symptomatic dengue virus infection with serotypes 2, 3, and 4 but not serotype 1. Science Translational Medicine. 2024. 16: eadn2199.
  • Bos S, Duarte EM, Lee NE, Zambrana JV, Graber AL, Balmaseda A, and Harris E. Order matters: DENV2-ZIKV and ZIKV-DENV2 sequential infections differently modulate the landscape of homotypic and DENV cross-reactive antibody responses. American Society of Tropical Medicine and Hygiene (ASTMH) Annual Meeting; 2024. Abstract 6008. https://d1lx8xdon3af7k.cloudfront.net/Abstract-Book-Abstracts-7501-8000.pdf
• Immune imprinting: each flavivirus infection leaves a unique fingerprint. The field long assumed that antigenically related flaviviruses produce similar antibody responses. I show that even within a single serocomplex each primary infection imprints a unique signature on the immune system, and this imprint conditions how subsequent infections are recognized and controlled. 
  • Singh T*, Bos S*, Vásquez Alemán G, Kim T, Walter M, Lee N, Duarte E, Graber A, Balakhmet A, Zambrana JV, Ruiz Salinas JA, Narvaez F, Balmaseda A, Kim E-Y, Wolinsky S, and Harris E. Multiple roads lead to Rome: B cell imprinting in distinct sequential flavivirus infections reveals different pathways to acquiring virus-neutralizing antibodies. The Journal of Immunology. 2025. 214(Supplement_1): vkaf283.2116.
  • Duarte EM, Bal A, Chapa MA, Sánchez San Martin C, Verdolin Jr M, Graber A, Mercado-Hernandez R, Kuan G, Balmaseda A, Bos S†, and Harris E†. Serotype-dependent fusion loop and prM antibody profiles in primary dengue virus infections. Communications Biology. In press.
• Antibody dynamics. My work also resolves antibody dynamics at the level of viral protein, domain, and epitope, defining how the quantity and quality of the antibody response evolve over time. I show that antibodies binding to different regions of a single protein have distinct dynamics, fundamentally changing how researchers think about long-term immunity. I also show that, in endemic settings, cross-reactive antibodies rise rather than wane after primary infection, challenging the assumption that decaying antibodies drive disease severity. 
  • Bos S* & Singh T* & Zambrana JV*, Duarte EM, Mercado-Hernandez R, Huffaker J, Graber A, Balmaseda A, and Harris E. Longitudinal antibody profiling after dengue reveals distinct dynamics by antibody specificity over 18 months. Nature Communications. 2026. 17(1): 7808.
• Rethinking and defining antibody correlates of protection against dengue: Identifying antibody features that predict protection versus severe disease remains central to dengue vaccine development. My work aims to develop and improve assays for correlates of protection spanning neutralization and Fc effector functions. Importantly, my work shows that correlates of protection are not universal across DENV serotypes. Complementary work identified IgA-driven neutrophil activation as a driver of severe post-Zika dengue, establishing antibody quality and effector function as correlates of protection and risk. 
  • Bos S*† & Graber AL*, Cardona-Ospina JA, Duarte EM, Zambrana JV, Ruíz Salinas JA, Mercado-Hernandez R, Singh T, Katzelnick LC, de Silva A, Kuan G, Balmaseda A, and Harris E†. Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype. Nature Communications. 2024. 15(1): 382.
  • Cardona-Ospina JA, Roy V, Marcano-Jiménez DE, Bos S, Duarte E, Zambrana JV, Bal A, Dias AG Jr, Zhiteneva J, Huffaker J, Montenegro C, Kuan G, Ramos-Benitez MJ, Balmaseda A, Alter G, and Harris E. IgA-driven neutrophil activation underlies post-Zika severe dengue disease in humans. Nature Immunology. 2026. 27: 126–134.