Oligomeric State of the ZIKV E Protein Defines Protective Immune Responses

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Oct 12

PMID 31601808

Citations 17

Authors

Stefan W Metz

Ashlie Thomas

Alex Brackbill

John Forsberg

Michael J Miley

Cesar A Lopez

Helen M Lazear

Shaomin Tian

Aravinda M de Silva

Affiliations

Soon will be listed here.

Abstract

The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines.

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