TY - JOUR
T1 - Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors
AU - López-Camacho, César
AU - Abbink, Peter
AU - Larocca, Rafael A.
AU - Dejnirattisai, Wanwisa
AU - Boyd, Michael
AU - Badamchi-Zadeh, Alex
AU - Wallace, Zoë R.
AU - Doig, Jennifer
AU - Velazquez, Ricardo Sanchez
AU - Neto, Roberto Dias Lins
AU - Coelho, Danilo F.
AU - Kim, Young Chan
AU - Donald, Claire L.
AU - Owsianka, Ania
AU - De Lorenzo, Giuditta
AU - Kohl, Alain
AU - Gilbert, Sarah C.
AU - Dorrell, Lucy
AU - Mongkolsapaya, Juthathip
AU - Patel, Arvind H.
AU - Screaton, Gavin R.
AU - Barouch, Dan H.
AU - Hill, Adrian V.S.
AU - Reyes-Sandoval, Arturo
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Zika 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 ΔTM 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.
AB - Zika 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 ΔTM 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.
U2 - 10.1038/s41467-018-04859-5
DO - 10.1038/s41467-018-04859-5
M3 - Article
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2441
ER -
