Table 1.
Summary of human DENV-specific monoclonal antibodies isolated from immune donors.
| References | Method | Efficiency | #Donors | mAbs isolated | Key findings |
|---|---|---|---|---|---|
| Schieffelin et al. (15) | B-cell immortalization (EBV) | N/A | 1 > 2 years post infection | 3 | DENV-specific MBCs were in circulation >2 years post exposure 2% of cultures were DENV2 specific All isolated mAbs were IgG1 |
| Beltramello et al. (14) | B-cell immortalization (EBV) with CpG Screened and cloned by limiting dilution. |
6.5–14% | 5 3-1° 2-2° 200 days to >8 years post-infection |
70 | All of the isolated mAbs were IgG: 68 IgG1, 1 IgG3, 1 IgG4 13 mAbs recognized EDIII and were the most potently neutralizing of all the mAbs isolated (5 serotype specific, 8 cross reactive) 34 mAbs recognized DI/DII they were highly cross reactive and less neutralizing, 6 mAbs recognized PrM, 11 mAbs recognized non-structural proteins, and 1 recognized capsid |
| Smith et al. (27) | B cells immortalized (EBV) with CpG and CHK2. Screened by ELISA. Positive wells fused to generate hybridomas. | >10-fold increase in the # of successful human hybridomas generated | 12 6–1° 6–2° 4–24 years post infection |
37 | 29/37 isolated mAbs recognized E protein, 26 were IgG1 and 3 were IgG2 26/37 isolated mAbs were cross reactive, most bound to EDI/II 5- isolated mAbs EDIII specific (1C7, 1M23, 2J20, 1B23, 1M19) all cross reactive 3-mAbs had moderate to strong neutralizing potency against at least one serotype (2D22, 5J7, 2J20) 8- isolated mAbs PrM specific, mAbs exhibited enhancing properties |
| Smith et al. (30) | B-cell immortalization (EBV) CpG and CHK2 Screened by ELISA and neutralization then fused to generate hybridomas |
N/A | 3 2–1° 1–2° 1–9 years post-infection |
50 | Most potently neutralizing mAbs bound to EDIII (1M7) or complex (1F4) epitopes on intact virions. DENV specific MBC frequency similar between primary and secondary donors at 14–18 DENV specific MBC per thousand B cells. 15 of the isolated mAbs were non-neutralizing, and bound to rE or PrM. |
| Cox et al. (25) | FACS using E (DENV2-80E) and dual labeled secondary antibodies Isolated double positive MBCs |
20 million PBMCs, 148 DENV E+ MBCs sorted. | 1 from an endemic region Serum neutralized all 4 serotypes | 9 | DENV E specific MBCs are present in naturally infected donors. Authors isolated and characterized DENV neutralizing mAbs from MBCs against envelope domain I and the fusion loop. Of the sorted MBCs following 2 week stimulation in culture 64% were positive for IgG, 20% were positive for DENV by ELISA, 8% secreted DENV2 specific mAbs Of the 9 mAbs isolated 1-non-neutralizing, 3-serotype-specific, 2-neutralized 2–3 serotypes 3-neutralized 4 serotypes. |
| Appanna et al. (28) | FACS using fluorescently labeled DENV3. Isolated DENV positive MBCs | N/A | 4 2° |
19 | 40–60% of the DENV-specific MBCs sorted bound to DENV Most mAbs isolated bound to complex epitopes, 24.4% bound to PrM and 17.8% bound to rE Majority were cross reactive and weakly neutralizing |
| Nivarthi et al. (31) | B-cell immortalization (EBV) CpG and CHK2 followed by fusion | N/A | 2 1° DENV-4 |
8 | Frequency of DENV-specific B-cells in circulation 0.19–0.2%. Of the 8 mAbs isolated, 2 neutralized DENV-4 and recognize regions on EDI/EDII hinge. |