Linear and Continuous Flavivirus Epitopes From Naturally Infected Humans

Abstract

This manuscript is an up-to-date review of experimentally validated linear and continuous epitopes identified from arbovirus members of the Flavivirus genus. We summarized 153 immunoreactive peptides from the Dengue virus, Zika virus, Japanese encephalitis virus, West Nile virus, and tick-borne encephalitis virus described in studies published from 1989 to 2020. We included peptides from structural (envelope, capsid, and pre-membrane) and nonstructural (Ns1–5) viral proteins that demonstrated relevant immunoreactivity with antibodies from naturally infected or vaccinated humans. We included peptides that demonstrated relevant reactivity features, such as indicators of disease severity related to immunological or immunopathological outcomes, differential or group diagnostic markers, immunotherapy candidates, and potential for vaccine formulation. The majority of immunoreactive peptides were described for DENV probably due to its long-lasting impact on human health and the lack of efficient vaccines and therapeutic methods. Immune landscape data regarding linear immunoreactive and continuous flavivirus peptides are still scarce, and a complete and more detailed map remains to be elucidated. Therefore, this review provides valuable data for those investigating the antibody response against flavivirus infection.

Linear epitope mapping in the E and NS1 proteins of dengue and Zika viruses: Prospection of peptides for vaccines and diagnostics

“…Peptides have shown significant potential in advancing the development of highly specific diagnostic tests and vaccines [ 16 – 18 ]. In the present study, we unveiled the epitope profile recognized by dengue and Zika patients in the E and NS1 proteins of both DENV and ZIKV, highlighting certain peptides that show promise for the development of serological tests for the differential diagnosis of dengue and Zika infections, as well as for the production of candidate vaccines.…”

Identification of Zika Virus NS1-Derived Peptides with Potential Applications in Serological Tests

“…For 2F2 mAb, the reactively identified epitopes were mostly conserved between ZIKV, DENV, WNV, and JEV in both linear and structural aspects. Previous studies have identified similar linear and discontinuous flavivirus epitopes from naturally infected humans [ 49 ]. The epitope REGYRT mapped on immunodominant region three of the NS1 loop has been previously described [ 42 ].…”

“…We believe the improved specificity of the pAbs in rabbit sera was conferred by the use of the C-terminal fragment of ZIKV-NS1 as the background for finding specific reactive epitopes [ 26 , 47 ]. We checked six distinct regions for highly reactive ZIKV, and only one region was detected with less intensity for DENV and YFV [ 49 ]. The ZIKV epitope EGYRTQV is located from immunodominant region three to the loop and from the epitopes LRSTTASGR (ZIKV) SLRTTTASG (DENV2), SLRTTTVSG (DENV3) to the immunodominant region four [ 42 ].…”

A Dual-Approach Strategy to Optimize the Safety and Efficacy of Anti-Zika Virus Monoclonal Antibody Therapeutics

“…This may lead to hyperinflammatory responses and cytokine storms, potentially causing lethal dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) [ 16 , 18 , 19 ]. Antibodies against the ZIKV E protein also carry the risk of exacerbating DENV symptoms via ADE as the E proteins of the two flaviviruses share many common epitopes [ 20 , 21 ]. Indeed, the ADE of DENV infection and disease severity through anti-ZIKV antibodies have been demonstrated both in vitro and in vivo [ 15 , 22 , 23 , 24 , 25 ].…”