Surrogate virus neutralization test as a scalable and reliable tool for immune surveillance in booster-vaccinated populations

Lin Cai; Zhaoyang Fang; Renyun Zha; Zhifeng Zhou; Ruiyin Zhang; Xueyun Li; Cheng Guo; Conghui Liao

doi:10.1038/s41598-026-49973-3

Surrogate virus neutralization test as a scalable and reliable tool for immune surveillance in booster-vaccinated populations

Sci Rep. 2026 May 2. doi: 10.1038/s41598-026-49973-3. Online ahead of print.

Authors

Lin Cai^#¹, Zhaoyang Fang^#², Renyun Zha², Zhifeng Zhou¹, Ruiyin Zhang¹, Xueyun Li³, Cheng Guo^{4

5}, Conghui Liao^{6

7}

Affiliations

¹ Shenzhen Futian District Center for Disease Control and Prevention, Shenzhen, 518040, China.
² School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
³ Shenzhen Futian District Center for Disease Control and Prevention, Shenzhen, 518040, China. ftcdcmy@163.com.
⁴ School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China. guoch36@mail.sysu.edu.cn.
⁵ National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, Guangzhou, 510080, China. guoch36@mail.sysu.edu.cn.
⁶ School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China. liaoch9@mail.sysu.edu.cn.
⁷ National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, Guangzhou, 510080, China. liaoch9@mail.sysu.edu.cn.

^# Contributed equally.

PMID: 42069915
DOI: 10.1038/s41598-026-49973-3

Abstract

With waning vaccine-induced immunity and the continued emergence of immune-evasive SARS-CoV-2 variants, booster vaccination has become essential for sustaining population-level protection. However, scalable and reliable serological tools for monitoring post-booster humoral immunity across different vaccine platforms remain insufficiently evaluated. We conducted a cross-sectional study and a booster cohort study to systematically compare the performance and concordance of surrogate virus neutralization test (sVNT), pseudovirus neutralization test (pVNT), and binding IgG antibody assays. In the cross-sectional analysis, serum samples from 259 individuals collected 1-2 months after a third dose of inactivated vaccine were used to compare sVNT and pVNT. In the booster cohort, paired sera from 288 participants receiving a fourth dose with different vaccine platforms were analyzed to evaluate the relationship between sVNT and IgG responses. Correlation and agreement were assessed using Spearman correlation and Bland-Altman analyses. In the cross-sectional study, sVNT showed strong concordance with pVNT, demonstrated by a very high correlation (r = 0.97) and good agreement in Bland-Altman analysis. In the booster cohort study, IgG antibody levels correlated strongly with sVNT overall (r = 0.91). The correlation strength remained highly consistent across different vaccine platforms, with no statistically significant differences observed. Collectively, these findings demonstrate that sVNT closely reflects functional neutralizing activity, supporting its utility for large-scale immune monitoring. sVNT offers an optimal balance of analytical performance and scalability for high-throughput monitoring without requiring cell-based assays. Consequently, we propose a tiered immune monitoring strategy: utilizing sVNT for broad population-level surveillance and reserving pVNT for targeted, precise functional assessment.

Keywords: Booster vaccination; Humoral immunity; Immune monitoring; Pseudovirus neutralization test; Surrogate virus neutralization test.

Abstract

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