A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus

Abstract

The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut50 ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.

Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response

“…One group reported the cloning of a germline-like mAb using a phage display from a naïve human antibody library [37]. Another group reported that a panel of germline-like antibodies was cloned from circulating plasmablasts of a ZIKV-infected patient 12 days after symptom onset [38]. These mAbs exhibited weak-to-moderate neutralizing potency.…”

“…These mAbs exhibited weak-to-moderate neutralizing potency. One mAb had no SHM capacity, but could nevertheless bind to an immunodominant epitope and neutralize ZIKV [38]. Most of the E-binding mAbs that we cloned, including all of the EDIII-targeted mAbs, had low SHM rates ( Figure 3B).…”

Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network

“…A human IgG mAb P1F12 was isolated from a ZIKV-infected individual (who developed GBS) in Brazil. Remarkably, despite being entirely germline-encoded, P1F12 exhibits high affinity and specificity for ZIKV and does not cross-react with any of the four DENV serotypes (Magnani et al, 2017). It appears that all ZIKV-infected individuals mount Ab responses against the epitope recognized by P1F12.…”

“…Z-Quick Test overview (Magnani et al, 2017). Ninety-six-well ELISA plates are coated with an anti-flavivirus mAb overnight.…”

Untold stories of the Zika virus epidemic in Brazil

“…Neutralization assays are more specific but still not clinically available, and molecular tests are restricted for use in a shorter window period after symptom initiation, if present. The development of point‐of‐care diagnostic tests that can be reliably used in areas with high incidence of other arboviruses is expected in the near future . Some mathematical models have suggested high seroprevalence in Northeast Brazil, but the data should be confirmed with other seroepidemiological surveys.…”