Antibody Quality and Protection from Lethal Ebola Virus Challenge in Nonhuman Primates Immunized with Rabies Virus Based Bivalent Vaccine

Abstract

We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

Post-exposure treatments for Ebola and Marburg virus infections

“…Nearly all these vaccines use filovirus glycoprotein (GP) as the protective immunogen. These vaccines completely protected NHPs against lethal disease and are mostly replication-defective or replication-competent viral vectors, including alphavirus replicons 241,242 , human adenoviruses [243][244][245][246][247] , chimpanzee adenoviruses 248 , paramyxoviruses 249,250 , rabies viruses 251,252 and several different strategies with recombinant vesicular stomatitis viruses (rVSVs), including both the prototype rVSV vaccine [253][254][255][256][257] and a newer rVSV vaccine developed for enhanced safety (VesiculoVax) 258 . Virus-like particles [259][260][261] , a biologically contained EBOV lacking viral protein 30 (VP30) 262 , DNA 244 and several combinations of vaccines that include DNA, modified vaccinia Ankara (MVA) and various adenoviruses can also completely protect NHPs from lethal filovirus disease 244,248,263 .…”

Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

“…Furthermore, pre-existing immunity against RABV did not impact the immunogenicity of these vaccines in mice [72]. Meanwhile, a replication-competent vaccine provided 100% protection against EBOV challenge, which was a better result than that achieved by the other two RABV vaccines [73]. Detailed investigation of adaptive immune responses showed that the successful ebolavirus vaccine could induce strong virus-specific antibodies [73].…”

“…Meanwhile, a replication-competent vaccine provided 100% protection against EBOV challenge, which was a better result than that achieved by the other two RABV vaccines [73]. Detailed investigation of adaptive immune responses showed that the successful ebolavirus vaccine could induce strong virus-specific antibodies [73]. However, more safety tests should be conducted before advancing the RABV-based vaccine to clinical trials.…”

Ebola vaccines in clinical trial: The promising candidates

“…In 2013, a study immunized NHPs with a platform based on replication competent RABV, replicationdeficient RABV, or chemically inactivated RABV expressing EBOV GP. 69 The live replication-competent vaccine provided 100% protection following EBOV challenge while the others provided 50% protection. The results indicated that the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP.…”