Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors
López-Camacho C., Abbink P., Larocca RA., Dejnirattisai W., Boyd M., Badamchi-Zadeh A., Wallace ZR., Doig J., Velazquez RS., Neto RDL., Coelho DF., Kim YC., Donald CL., Owsianka A., De Lorenzo G., Kohl A., Gilbert SC., Dorrell L., Mongkolsapaya J., Patel AH., Screaton GR., Barouch DH., Hill AVS., Reyes-Sandoval A.
AbstractZika virus (ZIKV) emerged on a global scale and no licensed vaccine ensures long-lasting anti-ZIKV immunity. Here we report the design and comparative evaluation of four replication-deficient chimpanzee adenoviral (ChAdOx1) ZIKV vaccine candidates comprising the addition or deletion of precursor membrane (prM) and envelope, with or without its transmembrane domain (TM). A single, non-adjuvanted vaccination of ChAdOx1 ZIKV vaccines elicits suitable levels of protective responses in mice challenged with ZIKV. ChAdOx1 prME ∆TM encoding prM and envelope without TM provides 100% protection, as well as long-lasting anti-envelope immune responses and no evidence of in vitro antibody-dependent enhancement to dengue virus. Deletion of prM and addition of TM reduces protective efficacy and yields lower anti-envelope responses. Our finding that immunity against ZIKV can be enhanced by modulating antigen membrane anchoring highlights important parameters in the design of viral vectored ZIKV vaccines to support further clinical assessments.