{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:13:42Z","timestamp":1786115622624,"version":"build-2736575974"},"reference-count":125,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007162","name":"Guangdong Provincial Science and Technology Plan Project-International Science and Technology Cooperation Field","doi-asserted-by":"publisher","award":["2025A0505020047"],"award-info":[{"award-number":["2025A0505020047"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016692","name":"Key Research and Development Program of Ningxia Hui Autonomous Region","doi-asserted-by":"crossref","award":["2026BEG02026"],"award-info":[{"award-number":["2026BEG02026"]}],"id":[{"id":"10.13039\/100016692","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2026BEG02026"],"award-info":[{"award-number":["2026BEG02026"]}],"id":[{"id":"https:\/\/ror.org\/015bdn754","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Virus-specific antibody responses, including binding antibodies and neutralizing antibodies (nAbs), are important indicators of antiviral immune status after infection or immunization. They provide complementary information on antiviral humoral immunity after infection or vaccination. Antigen-binding antibodies indicate previous exposure and the magnitude of the immune response, whereas receptor-blocking and functional neutralization assays assess whether antibodies interfere with viral entry or infection. Conventional neutralization assays, such as plaque reduction neutralization tests and pseudovirus neutralization tests, provide functional information but are labor-intensive, time-consuming, biosafety-restricted, and difficult to deploy for large-scale or decentralized monitoring. Paper-based biosensors, including lateral flow assays (LFAs), microfluidic paper-based analytical devices (\u03bcPADs), and paper-based ELISA, have emerged as promising point-of-care tools owing to their low cost, portability, simple operation, and compatibility with visual or digital readouts. This review critically evaluates these platforms according to whether they measure antigen-binding antibodies, receptor-blocking activity, surrogate neutralization, or functional neutralization and summarizes the applications of these three platforms for monitoring antibody responses against SARS-CoV-2, influenza, dengue, Zika, and monkeypox viruses. Unlike previous reviews that mainly focus on general paper-based biosensor design or conventional nAb assays, this review emphasizes the distinction between antigen-binding, receptor-blocking, and surrogate neutralization readouts, and critically discusses how paper-based signals should be interpreted in relation to functional immunity. We further analyze key translational challenges, including quantitative accuracy, antigen cross-reactivity, standardization, clinical validation, regulatory positioning, and real-world implementation. Future development should combine multiplex detection, standardized calibration, digital and AI-assisted interpretation, and clinically validated assay formats. Paper-based biosensors have considerable potential for decentralized antibody monitoring and public health surveillance, but their clinical utility depends on clear assay positioning and validation against appropriate functional or reference methods.<\/jats:p>","DOI":"10.3390\/bios16080420","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:15:22Z","timestamp":1785834922000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paper-Based Biosensors for Monitoring Binding, Blocking, and Surrogate Neutralizing Antibody Responses Against Viral Infections"],"prefix":"10.3390","volume":"16","author":[{"given":"Yiren","family":"Yin","sequence":"first","affiliation":[{"name":"BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Ministry of Education, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Yi","sequence":"additional","affiliation":[{"name":"BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Ministry of Education, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazheng","family":"Yu","sequence":"additional","affiliation":[{"name":"BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Ministry of Education, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7272-4521","authenticated-orcid":false,"given":"Tatyana Aleksandrovna","family":"Khrustaleva","sequence":"additional","affiliation":[{"name":"Multidisciplinary Diagnostic Laboratory, Institute of Physiology, National Academy of Sciences of Belarus, 220072 Minsk, Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Zhai","sequence":"additional","affiliation":[{"name":"BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Ministry of Education, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2986-8028","authenticated-orcid":false,"given":"Jianhai","family":"Yu","sequence":"additional","affiliation":[{"name":"BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Ministry of Education, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Ministry of Education, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Shen","sequence":"additional","affiliation":[{"name":"BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Ministry of Education, Guangzhou 510515, China"},{"name":"Key Laboratory of Infectious Diseases Research in South China, State Key Laboratory of Muti-Organ Injury Prevention and Treatment, Southern Medical University, Ministry of Education, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11751","DOI":"10.1021\/acs.analchem.4c01165","article-title":"Semiquantitative Paper-Based Microfluidic Surrogate Virus Neutralization Test for SARS-CoV-2 Neutralizing Antibodies","volume":"96","author":"Mahmud","year":"2024","journal-title":"Anal. 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