Abstract
ABSTRACT In the last few decades, Ebola virus (EBOV) has emerged periodically and infected people in Africa, resulting in an extremely high mortality rate. With no available prophylaxis or cure so far, a highly effective Ebola vaccine is urgently needed. In this study, we developed a novel chimpanzee adenovirus-based prime-boost vaccine by exploiting two recombinant replication-deficient chimpanzee adenoviral vectors, AdC7 and AdC68, which express glycoproteins (GP) of the EBOV strain identified in the 2014 outbreak. Our results indicated that a single immunization using AdC7 or AdC68 could stimulate potent EBOV-specific antibody responses, whereas the AdC7 prime-AdC68 boost regimen induced much stronger and sustained humoral and cellular immune responses in both mice and rhesus monkeys, compared with AdC7 or AdC68 single vaccination or the AdC68 prime-AdC7 boost regimen. This prime-boost vaccine could also protect mice from the simulated infection with EBOV-like particle (EBOVLP) in biosafety level 2 (BSL-2) laboratories, and antibodies from the prime-boost immunized rhesus macaques could passively provide protection against EBOVLP infection. Altogether, our results show that the AdC7 prime-AdC68 boost vaccine is a promising candidate for further development to combat EBOV infections.
Highlights
As a single-stranded RNA filovirus, Ebola virus (EBOV) causes the severe Ebola virus disease (EVD) and subsequently led to an extremely high mortality rate in the last four decades, since its discovery in 1976 [1–3]
The codon-optimized GP sequence under the regulation of cytomegalovirus (CMV) promoter was cloned into the E1-deleted region (ΔE1) of adenoviral vectors, AdC7 and AdC68, respectively (Supplementary Figure 1A)
AdC7empty and AdC68-empty viruses with no insertion in ΔE1 were generated as negative controls using the same amplification method
Summary
As a single-stranded RNA filovirus, Ebola virus (EBOV) causes the severe Ebola virus disease (EVD) and subsequently led to an extremely high mortality rate in the last four decades, since its discovery in 1976 [1–3]. A variety of EBOV vaccine candidates have been developed in past 10 years, and some of them have reached the clinical trial stage, including DNA vaccines [7], virus-like particle (VLP) based vaccines [8], recombinant vesicular stomatitis virus (rVSV) vectored vaccines [9], recombinant adenoviral vaccines [10,11], and modified vaccinia Ankara (MVA) vectored vaccines [11–13] Among these vaccine candidates, an rVSV vector-based live attenuated Ebola vaccine developed by Merck & Co. Inc was submitted for a US Food and Drug Administration (FDA) license approval [14]. In 2017, the China FDA approved an Ebola vaccine based on an adenoviral vector originated from human adenovirus serotype 5 (Ad5) [15] These two types of vaccines have provided basic support for the prevention and control of an Ebola epidemic in some cases. The heterologous primeboost strategy represents an innovative approach to fulfil this need [16]
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