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Identifying protective determinants is difficult because ASF virus (ASFV) is a large and complex DNA virus encoding over 160 proteins. Here, we constructed an ASFV proteome microarray containing 160 full-length proteins for profiling ASFV-specific antibodies. An antibody reactome containing 46 ASFV proteins (including 12 newly recognized B-cell antigens) was established by analyzing several cohorts of serum samples from pigs protected with different live-attenuated vaccines (LAVs). A proteome-wide study of antibody dynamics over a 26-day period provided a multi-dimensional landscape of the host humoral response against ASFV after acute infection, LAV immunization, and post-vaccination challenge. This study provides a comprehensive understanding of ASFV-induced humoral immune responses, highlights B-cell antigen candidates for vaccine design, supports the investigation of LAV protection mechanisms, and would accelerate vaccine development.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>African swine fever (ASF) poses a severe threat to global swine industries, with vaccine development hindered by limited understanding of immune protection. A comprehensive understanding of antibody responses against ASF virus (ASFV) and the discovery of protective antigens are fundamental to vaccine development. This study constructed an ASFV proteome microarray to profile antibody responses against 160 viral proteins and established the antibody spectra against ASFV with dynamic features. The proteome microarray offers a high-throughput platform for understanding ASFV immunology and pathogenicity and will contribute to ASF vaccine development and diagnosis.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00478-25","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T13:06:15Z","timestamp":1755176775000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["An African swine fever virus-specific antibody reactome reveals antigens as potential candidates for vaccine development"],"prefix":"10.1128","volume":"99","author":[{"given":"Songxin","family":"Guo","sequence":"first","affiliation":[{"name":"Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences","place":["Wuhan, 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