A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates

Abstract

<p id="P3">Zika virus (ZIKV) causes severe neurologic complications and fetal aberrations. Vaccine development is hindered by potential safety concerns due to antibody cross-reactivity with dengue virus and the possibility of disease enhancement. In contrast, passive administration of anti-ZIKV antibodies engineered to prevent enhancement may be safe and effective. Here, we report on human monoclonal antibody Z021, a potent neutralizer that recognizes an epitope on the lateral ridge of the envelope domain III (EDIII) of ZIKV and is protective against ZIKV in mice. When administered to macaques undergoing a high-dose ZIKV challenge, a single anti-EDIII antibody selected for resistant variants. Co-administration of two antibodies, Z004 and Z021, which target distinct sites on EDIII, was associated with a delay and a 3- to 4-log decrease in peak viremia. Moreover, the combination of these antibodies engineered to avoid enhancement prevented viral escape due to mutation in macaques, a natural host for ZIKV. </p><p id="P4">Passive administration of anti-Zika human monoclonal antibodies could be an efficacious and safe alternative to vaccines for at-risk populations. Keeffe et al. show that administration of a combination of two monoclonal antibodies to macaques followed by high-dose intravenous Zika challenge reduces viremia and prevents the emergence of viral escape mutations. </p><p id="P5"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/798fcd02-26bb-4b5b-b2a4-af77080b3e4b/PubMedCentral/image/nihms-1512146-f0001.jpg"/> </div> </p>