Novel Ebola Vaccine Induced Therapeutic Antibody In Primates

The 2014 ebolavirus outbreak has paralyzed the public health system in West Africa and caused global pandemic, while no effective antiviral strategy is available. Antibody therapy is positive and an effective way, which has more than one hundred years of history in controlling the emerging virulent infectious diseases, such as early treatment of measles,hepatitis A and the convalescent plasma treatment against Ebola infection, H1N1 and H5N1 infection. However, there are still some problems for the use of convalescent plasma,including safety, the limited supply, and poor cross-reactivity ability. In this study, therefore,we raised a concept that multiple immunization with the non-human primates such as:Rhesus Macaque whose antibody germline sequences are highly homologous to human immunoglobulin genes may facilitate the generation of high affinity human-like antibodies.In our previous work, adenovirus vectored vaccines against Zaire, Sudan and Marburg virus had been developed. Here, we continued to develop a new Bundibugyo ebolavirus vaccine based on type 2 adenovirus vector (rAd2-BEBOV GP). The results showed that the codon-optimized Bundibugyo Ebola virus GP gene was successfully cloned into the viral vector and efficiently expressed in Vero cells. Next, we compared three kinds of Ebola candidate vaccines, adenovirus vector vaccine, GP protein vaccine and Ebola virus-like particle vaccine (eVLP) in their capability of inducing antibody response by enzyme-linked immunosorbent assay (ELISA) and pseudotyped ebolavirus neutralization assasy. We found that adenovirus vector vaccine could rapidly induce high levels of binding antibodies and neutralizing antibodies in mice and Chinese rhesus monkeys, no matter at single or two immunizations. Furtherly, to obtain broadly neutralizing anti-sera, Chinese macaques were repeatly immunized with virous subtypes of adenovirus vector vaccine and boosted with GP protein vaccine and eVLP vaccine. Subsequently, we purified these immunoglobulin by the AKTA protein purification system with optimized purification system. Results show that the purified IgG has a high recovery rate and retain a high neutralizing activity. Due to a high homology, our purified IgG may reduce the toxicity of a heterologous protein. More importantly, the primate immunoglobulin IgG can be used as sympathetic treatment in emerging case of an epidemic with more than one circulating EBOV strains. This study supplied an important strategy for the Ebola epidemic prevention and provided a polyclonal therapeutic antibody resource for the "cocktail" treatment strategy against infectious diseases.