Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico

Abstract

Summary Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals that develop high titers of anti-ZIKV antibodies we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with preexisting reactivity to DENV1 in humans.

Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction

“…In addition to acute infection, persistent infections have been reported for ZIKV, as well as other flaviviruses [64][65][66]. Prolonged excretion of ZIKV in sperm and urine has also been reported [67,68].…”

Monoclonal Antibodies against Zika Virus: Therapeutics and Their Implications for Vaccine Design

“…The proportion of ZIKV-specific MAbs is further increased in focusing on the MAbs with in vivo protective efficacy. Six MAbs are ZIKV specific, while three are cross-protective against other flaviviruses (8)(9)(10)(12)(13)(14). This indicates that the ZIKV-specific MAbs display higher neutralizing activities and protection efficacies against ZIKV infection than cross-binding MAbs.…”

“…Z006, isolated from another patient, also bound to the LRs and is a strong neutralizer of both ZIKV and DENV serotype 1 virus (DENV-1) (Fig. 1E) (8).…”

“…Interestingly, the proportions of ZIKV-specific MAbs in the MAb groups differ. Among the 153 tested MAbs, 63 specifically bind to ZIKV E protein (E MAbs) (8)(9)(10)(11)(12)(13)(14), while 45 of 70 MAbs that convey 50% inhibition of the virus at a concentration of Ͻ1 g/ml are specific to ZIKV (8)(9)(10)(11)(12)(13)(14). The proportion of ZIKV-specific MAbs is further increased in focusing on the MAbs with in vivo protective efficacy.…”

A Bioinformatic Glimpse of Human-Origin Zika Virus Polyprotein

“…ZIKV is known to induce antibody-mediated and cell-mediated immunological responses [13,14]. Most significant to the bioinformatic parameters reported here, polyprotein amino acid 1118 is a component of a putative 20-mer conformational epitope (CE6) that has been reported [15] for polyprotein amino acids 1105-1124.…”