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Fig GIT mice have decreased bone
PBMC samples in this study were collected from patients at the acute phase (5–8 days after the onset of fever) or at the convalescent phase (12–19 days for convalescent phase) of secondary infection. This study enabled us to compare the efficiency of obtaining HuMAbs at each stage. From the acute-phase PBMCs, 81.8% anti-E, 6.6% anti-prM, and 3.3% anti-NS1 HuMAbs were obtained, while 13.3% anti-E, 13.3% anti-prM, and 53.3% anti-NS1 HuMAbs were obtained from convalescent-phase PBMCs. Several groups have used PBMCs from convalescent-phase, but not acute-phase, patients to prepare HuMAbs by immortalizing patient-derived ICG001 with EB virus. Dejnirattisai et al. [16] observed that 89% of anti-E HuMAbs were cross-reactive with all four serotypes. Surprisingly, their studies resulted in the preparation of more anti-prM than anti-E HuMAbs. Beltramello et al. [17] performed a large screen to gain insights into the domain specificity and cross-reactivity of E domain III-specific antibodies. A study by de Alwis et al. [18] showed that the efficiency of preparation of DENV complex cross-reactive neutralizing HuMAbs was significantly higher in secondary infection cases. Indeed, Beltramello et al. [17] differentiated their HuMAbs into two categories: those that recognized the DENV E domain III and showed complex cross-reactive neutralization activity, and those that recognized domain I/domain II and were more broadly cross-reactive but showed lower neutralization activity. Furthermore, our data in monomer study is the first to report the efficient preparation of HuMAbs with strong neutralization activity against all four DENV serotypes, using PBMCs from acute-phase patients secondarily infected with DENV.





 
 
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