Adenoviral vector type 26 encoding Zika virus (ZIKV) M-Env antigen induces humoral and cellular immune responses and protects mice and nonhuman primates against ZIKV challenge.

Freek Cox,Ella Van Huizen,Janneke Verhagen,Dan H Barouch,Roland Zahn,Jeroen Tolboom,Hanneke Schuitemaker,Eirikur Saeland,Leslie Van Der Fits,Baerbel Kaufmann,Rafael A Larocca,Peter Abbink,Rebecca Peterson,Eliane N Miyaji

doi:10.1371/journal.pone.0202820

Freek Cox, Ella Van Huizen + Show 12 more

Open Access

https://doi.org/10.1371/journal.pone.0202820

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Abstract

In 2015, there was a large outbreak of Zika virus (ZIKV) in Brazil. Despite its relatively mild impact on healthy adults, ZIKV infection during pregnancy has been associated with severe birth defects. Currently, there is no ZIKV vaccine available, but several vaccine candidates based on the ZIKV membrane (M) and envelope (Env) structural proteins showed promising results in preclinical and clinical studies. Here, the immunogenicity and protective efficacy of a non-replicating adenoviral vector type 26 (Ad26) that encodes the ZIKV M-Env antigens (Ad26.ZIKV.M-Env) was evaluated in mice and non-human primates (NHP). Ad26.ZIKV.M-Env induced strong and durable cellular and humoral immune responses in preclinical models. Humoral responses were characterized by Env-binding and ZIKV neutralizing antibody responses while cellular responses were characterized by ZIKV reactive CD4+ and CD8+ T cells. Importantly, a single immunization with a very low dose of 4x107 vp of Ad26.ZIKV.M-Env protected mice from ZIKV challenge. In NHP, a single immunization with a typical human dose of 1x1011 vp of Ad26.ZIKV.M-Env also induced Env-binding and ZIKV neutralizing antibodies and Env and M specific cellular immune responses that associated with complete protection against viremia from ZIKV challenge as measured in plasma and other body fluids. Together these data provide the rationale to progress the Ad26.ZIKV.M-Env candidate vaccine to clinical testing.

Highlights

Zika virus (ZIKV) is a mosquito-borne virus that was thought to be restricted to Africa and South-East Asia
We show that adenoviral vector type 26 (Ad26) encoding for ZIKV M and Env is highly immunogenic in several preclinical models
Ad26.ZIKV.M and Env antigens (M-Env) induced strong humoral immune responses in mice and non-human primates (NHP) that were characterized by antibodies capable of binding the ZIKV Env protein, and in vitro neutralization of the vaccine-heterologous ZIKV-PR strain

Summary

Introduction

Zika virus (ZIKV) is a mosquito-borne virus that was thought to be restricted to Africa and South-East Asia. In 2016 the Brazil outbreak was characterized by an association with serious birth defects in infants born to women who became ZIKV infected during pregnancy [3]. It was previously reported that vaccination with a rhesus macaque replication-incompetent adenovirus vector type 52 (RhAd52) encoding the ZIKV membrane protein (M) and the ZIKV envelope antigen (Env) lacking the peptide precursor (pr) (amino acids 216–794 of the polyprotein, RhAd52-M-Env) derived from the ZIKV strain BeH815744 elicited protective immunity against ZIKV challenge in mice and NHP [8,9]. We describe immunogenicity and protective efficacy in mice and NHP of a recombinant Ad26-based ZIKV vaccine candidate encoding the M-Env antigens (Ad26.ZIKV.M-Env) produced on the human PER.C61 cell line. Full protection against ZIKV challenge was achieved in mice that received a single immunization with a very low dose of Ad26.ZIKV.M-Env and in NHP that received a single immunization with a human dose of Ad26.ZIKV.M-Env

Results

Discussion

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