Vaccine redesign may separate Zika protection from risk of worsening dengue
A fusion-loop-engineered vaccine against the Zika virus (ZIKV) has shown promise in a nonhuman primate model. The research was reported in Cell Reports Medicine on Oct. 7.
A fusion-loop-engineered Zika vaccine has shown promise in nonhuman primates, according to a study published in Cell Reports Medicine. Researchers at the Institute of Microbiology of the Chinese Academy of Sciences and the Institute of Medical Biology of the Chinese Academy of Medical Sciences redesigned the viral envelope protein's fusion loop to stimulate protective antibodies while minimizing the risk of antibody-dependent enhancement (ADE).
ADE is a concern in flavivirus vaccine development, as it can worsen infection instead of preventing it. The study's lead authors, Dai Lianpan and George F. Gao, found that over 97% of the vaccine-induced B cells were ZIKV-specific, dominated by a convergent population using a germline ortholog of human IGHV5-10-1. Antibodies from this population blocked multiple stages of viral entry and targeted a distinct, vulnerable hotspot on ZIKV.
Importantly, these antibodies do not cross-react with dengue virus due to the absence of a homologous glycan that imposes steric shielding. These findings support the redesign of Zika vaccines to preserve protection while reducing the risk of dengue antibody-dependent enhancement.
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