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Updated: Nov 28, 2025
Quantification of Antibody-dependent Enhancement of the Zika Virus in Primary Human Cells
Published on: January 18, 2019
Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections
Madhumati Sevvana1, Thomas F Rogers2, Andrew S Miller1
1Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Abstract:
Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV's "Achilles heel", defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies.
Insights
A new study reveals the structure of Zika virus (ZIKV) bound to a neutralizing antibody, ADI-30056. This finding identifies a critical viral target for developing effective ZIKV therapeutics and vaccines.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Zika virus (ZIKV), a mosquito-borne flavivirus, causes severe neurological disorders like microcephaly.
- Developing effective vaccines and therapeutics against ZIKV is a global health priority.
Purpose of the Study:
- To determine the high-resolution structure of ZIKV in complex with a specific neutralizing human monoclonal antibody (hMAb), ADI-30056.
- To identify the structural basis for antibody-mediated ZIKV neutralization and potential therapeutic targets.
Main Methods:
- X-ray crystallography was used to obtain a 4.0 Å resolution structure of the ZIKV-ADI-30056 complex.
- Structure-based functional analysis and sequence comparisons were performed.
Main Results:
- The structure revealed that ADI-30056 binds across E protein dimers on the ZIKV surface.
- This binding inhibits conformational changes necessary for viral fusion and infection, similar to another known antibody, ZIKV-117.
- Key ZIKV residues essential for neutralization and antibody evolution were identified.
Conclusions:
- The identified epitope, targeted by ADI-30056, represents a vulnerable site on ZIKV, termed its "Achilles heel".
- This epitope is a promising target for the rational design of novel therapeutic antibodies against Zika virus.
