Abstract
The incidence of dengue virus (DENV) infections has been escalating in tropical and subtropical countries, but there are still no effective therapeutic options. In the present study, a DENV-1-specific human monoclonal antibody (HMAb), 1G5, isolated from single plasma cells obtained from the peripheral blood mononuclear cells of dengue patients was found to have potent neutralization activity against serotype 1 DENV (DENV-1). Its neutralization activity against DENV-2 was not as strong, and it was almost absent for DENV-3 and DENV-4. The results showed that HMAb 1G5 only binds to the envelop protein of intact DENV-1 or the envelop protein under unheated and non-reducing conditions, and that it does not bind to recombinant envelope protein. This could mean that the antibody recognizes a conformational epitope of the envelope protein. Further, the findings showed that HMAb 1G5 potently neutralizes DENV-1 in both the pre- and post-attachment phases of the virus at low concentrations. In vivo studies showed that HMAb 1G5 provides protection from DENV-1 infection in a murine model. In addition, antibody-dependent enhancement that occurs at lower doses of the antibody was completely abrogated by the introduction of Leu-to-Ala mutations (1G5-LALA) or deletion of nine amino acids (1G5-9del) in the Fc region. Therefore, HMAb 1G5 shows promise as a safe and effective agent for prophylactic and therapeutic treatment of DENV-1 infection.
Highlights
Dengue virus (DENV), which belongs to the Flaviviridae family, is an important arthropod-borne virus that targets humans
88 antibodies specific to dengue virus (DENV) were isolated by an enzyme-linked immunosorbent assay (ELISA); the inactivated dengue virion was used as the coating antigen
We found that human monoclonal antibody (HMAb) 1G5 recognized the E protein of DENV-1 and DENV-2, but it did not react with DENV-3 or DENV-4 (Figure 1A)
Summary
Dengue virus (DENV), which belongs to the Flaviviridae family, is an important arthropod-borne virus that targets humans. DENV infection is Neutralization of DENV-1 by HMAb 1G5 mainly prevalent in tropical and sub-tropical regions, with the highest incidence rates reported in the Americas, Eastern Mediterranean, Southeast Asia, and the Western Pacific regions. Different serotypes of DENV can cause epidemics in different regions of the world at the same time. The circulation of DENV-1 and DENV-2 serotypes in the Western Pacific region was reported in 20171. All four serotypes of DENV can cause epidemics in the same region; for example, in Guangdong Province, China, there has been outbreak of all four serotypes of DENV, DENV-1 was the predominant strain (Wu et al, 2011; Jiang et al, 2012; Zhao et al, 2012a,b). Dengue is a threat in southern China, where 46864 cases and six associated deaths were reported in 20142
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