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Accuracy, efficacy and safety of dengue CYD-TDV pre-vaccination screening with 5 existing IgG serotests: Retrospective analysis of phase III trials

2020; Elsevier BV; Volume: 101; Linguagem: Inglês

10.1016/j.ijid.2020.09.1254

1878-3511

Carlos A. DiazGranados, Matthew Bonaparte, Yaniv Lustig, Rémi Forrat, Gustavo H. Dayan, H. Wang, Ming Zhu, Shekema Hodge, Eli Schwartz, Yasemin Ataman‐Önal, Stephen J. Savarino,

Viral Infections and Vectors

Background: Post-hoc analyses of CYD-TDV vaccine efficacy trials indicated that dengue seropositive vaccinees experienced protection against dengue hospitalization and severe dengue, while seronegative vaccinees were at increased risk for these outcomes. Pre-vaccination screening has been recommended by WHO to identify those with prior dengue infection (PDI) who would benefit from vaccination. We retrospectively assessed the concept of pre-vaccination screening by estimating vaccine efficacy (VE) in test-positive individuals using five marketed serotests. Methods and materials: Pre-vaccination sera obtained from subjects in the immunogenicity subsets of CYD14 and CYD15 (n ≥ 3841) were tested by two ELISAs and three rapid diagnostic tests (RDT). Reference serostatus was determined using measured dengue PRNT90, PRNT50 and NS1 IgG ELISA pre-vaccination, enabling estimation of serotest performance. VE against symptomatic virologically-confirmed dengue (VCD) over 25 months and dengue hospitalization over 6 years from first injection was assessed in test+ subjects using a Cox regression model. Pooled VE [(1 − Hazard Ratio) × 100] across all ages (2–16 years) is presented. Results: Assay specificity was high for all tests: Euroimmun-IgG-ELISA, 98.8% (95% CI: 97.9–99.3); Panbio-Indirect-IgG-ELISA, 99.2% (98.5–99.6); Biocan-RDT, 99.0%(98.3–9.5); SDBioline-RDT, 96.0% (94.8–97.1); and CTK-RDT, 99.5% (98.9–99.8). Sensitivity of the Euroimmun-ELISA (89.2%[87.9–90.3]) and Panbio-ELISA (92.5% [91.4–93.5]) were substantially higher than that of the SDBioline-RDT (71.1% [69.3–72.8]), Biocan-RDT (52.5% [50.6–54.4]) and CTK-RDT (47.6% [45.7–49.5]). For each serotest, vaccination of test+ subjects was associated with high VE against VCD (Table 1). Significant protection against hospitalized VCD was evident for test+ subjects with each serotest except CTK-RDT, for which the estimate was favorable, but the lower 95% CI crossed the null.Table 1VE against VCD and dengue hospitalization in test+ subjects.EndpointImmunoassayaIgG readout only.IncidencebCases/100 person-years. (95% CI)VE (95% CI)CYD-TDVPlaceboVCD (25 months)ELISA-Euroimmun0.4 (0.2–0.6)3.0 (2.2–4.0)88.3 (77.4–93.9)ELISA-Panbio0.4 (0.2–0.6)3.0 (2.2–3.9)87.6 (76.7–93.4)RDT-Biocan0.2 (0.1–0.6)2.0 (1.2–3.0)88.8 (66.9–96.2)RDT-SDBioline0.5 (0.2–0.8)2.7 (1.9–3.8)82.8 (66.9–91.1)RDT-CTK0.2 (0.0–0.5)1.7 (1.0–2.8)89.7 (64.6–97.0)Hospitalized VCD (6 years)ELISA-Euroimmun0.1 (0.0–0.2)0.4 (0.2–0.6)72.8 (38.9–87.9)ELISA-Panbio0.1 (0.1–0.2)0.5 (0.3–0.7)77.5 (52.8–89.3)RDT-Biocan<0.1 (0.0–0.1)0.3 (0.1–0.5)92.4 (37.8–99.1)RDT-SDBioline<0.1 (0.0–0.1)0.3 (0.2–0.6)87.2 (54.5–96.4)RDT-CTK<0.1 (0.0–0.2)0.2 (0.1–0.5)73.7 (−5.1 to 93.4)a IgG readout only.b Cases/100 person-years. Open table in a new tab Conclusion: Using five dengue IgG immunoassays, vaccination of test+ subjects is evidently safe and efficacious. The more sensitive ELISAs offer the distinct advantage of identifying a larger proportion of individuals who would benefit from vaccination.