RT Journal Article SR Electronic(1) A1 Li, Xiao-Quan A1 Qiu, Li-Wen A1 Chen, Yue A1 Wen, Kun A1 Cai, Jian-Piao A1 Chen, Jing A1 Pan, Yu-Xian A1 Li, Jie A1 Hu, Dong-Mei A1 Huang, Yan-Fen A1 Liu, Li-Dong A1 Ding, Xi-Xia A1 Guo, Yong-hui A1 Che, Xiao-YanYR 2013 T1 Dengue virus envelope domain III immunization elicits predominantly cross-reactive, poorly neutralizing antibodies localized to the AB loop: implications for dengue vaccine design JF Journal of General Virology, VO 94 IS 10 SP 2191 OP 2201 DO https://doi.org/10.1099/vir.0.055178-0 PB Microbiology Society, SN 1465-2099, AB Dengue virus (DENV) is a mosquito-borne virus that causes severe health problems. An effective tetravalent dengue vaccine candidate that can provide life-long protection simultaneously against all four DENV serotypes is highly anticipated. A better understanding of the antibody response to DENV envelope protein domain III (EDIII) may offer insights into vaccine development. Here, we identified 25 DENV cross-reactive mAbs from immunization with Pichia pastoris-expressed EDIII of a single or all four serotype(s) using a prime–boost protocol, and through pepscan analysis found that 60 % of them (15/25) specifically recognized the same highly conserved linear epitope aa 309–320 of EDIII. All 15 complex-reactive mAbs exhibited significant cross-reactivity with recombinant EDIII from all DENV serotypes and also with C6/36 cells infected with DENV-1, -2, -3 and -4. However, neutralization assays indicated that the majority of these 15 mAbs were either moderately or weakly neutralizing. Through further epitope mapping by yeast surface display, two residues in the AB loop, Q316 and H317, were discovered to be critical. Three-dimensional modelling analysis suggests that this epitope is surface exposed on EDIII but less accessible on the surface of the E protein dimer and trimer, especially on the surface of the mature virion. It is concluded that EDIII as an immunogen may elicit cross-reactive mAbs toward an epitope that is not exposed on the virion surface, therefore contributing inefficiently to the mAbs neutralization potency. Therefore, the prime–boost strategy of EDIII from a single serotype or four serotypes mainly elicited a poorly neutralizing, cross-reactive antibody response to the conserved AB loop of EDIII., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.055178-0