Immunogenicity and Efficacy of Zika Virus Envelope Domain III in DNA, Protein, and ChAdOx1 Adenoviral-Vectored Vaccines
César López-Camacho,
Giuditta De Lorenzo,
Jose Luis Slon-Campos,
Stuart Dowall,
Peter Abbink,
Rafael A. Larocca,
Young Chan Kim,
Monica Poggianella,
Victoria Graham,
Stephen Findlay-Wilson,
Emma Rayner,
Jennifer Carmichael,
Wanwisa Dejnirattisai,
Michael Boyd,
Roger Hewson,
Juthathip Mongkolsapaya,
Gavin R. Screaton,
Dan H. Barouch,
Oscar R. Burrone,
Arvind H. Patel,
Arturo Reyes-Sandoval
Affiliations
César López-Camacho
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7BN, UK
Giuditta De Lorenzo
MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK
Jose Luis Slon-Campos
Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy
Stuart Dowall
Public Health England, National Infection Service, Porton Down, Salisbury SP4 0JG, UK
Peter Abbink
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Rafael A. Larocca
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Young Chan Kim
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7BN, UK
Monica Poggianella
Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy
Victoria Graham
Public Health England, National Infection Service, Porton Down, Salisbury SP4 0JG, UK
Stephen Findlay-Wilson
Public Health England, National Infection Service, Porton Down, Salisbury SP4 0JG, UK
Emma Rayner
Public Health England, National Infection Service, Porton Down, Salisbury SP4 0JG, UK
Jennifer Carmichael
MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK
Wanwisa Dejnirattisai
MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK
Michael Boyd
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Roger Hewson
Public Health England, National Infection Service, Porton Down, Salisbury SP4 0JG, UK
Juthathip Mongkolsapaya
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Gavin R. Screaton
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Dan H. Barouch
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Oscar R. Burrone
Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy
Arvind H. Patel
MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK
Arturo Reyes-Sandoval
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7BN, UK
The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the dengue virus, which has close similarities with ZIKV-EDIII, this antigen might not be a suitable vaccine candidate for the correct induction of protective immune responses against ZIKV.
